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With a broader range of entries than any other reference book on stage directors, this Encyclopedia showcases the extraordinary diversity of theatre as a national and international artistic medium. Since the mid nineteenth century, stage directors have been simultaneously acclaimed as prime artists of the theatre and vilified as impediments to effective performance. Their role may be contentious but they continue to exert powerful influence over how contemporary theatre is made and engaged with. Each of the entries - numbering over 1,000 - summarises a stage director's career and comments on the distinctive characteristics of their work, alluding to broader traditions where relevant. With an introduction discussing the evolution of the director's role across the globe and bibliographic references guiding further reading, this volume will be an invaluable reference work for stage directors, actors, designers, choreographers, researchers, and students of theatre seeking to better understand how directors work across different cultural traditions.
It remains unclear which individuals with subthreshold depression benefit most from psychological intervention, and what long-term effects this has on symptom deterioration, response and remission.
Aims
To synthesise psychological intervention benefits in adults with subthreshold depression up to 2 years, and explore participant-level effect-modifiers.
Method
Randomised trials comparing psychological intervention with inactive control were identified via systematic search. Authors were contacted to obtain individual participant data (IPD), analysed using Bayesian one-stage meta-analysis. Treatment–covariate interactions were added to examine moderators. Hierarchical-additive models were used to explore treatment benefits conditional on baseline Patient Health Questionnaire 9 (PHQ-9) values.
Results
IPD of 10 671 individuals (50 studies) could be included. We found significant effects on depressive symptom severity up to 12 months (standardised mean-difference [s.m.d.] = −0.48 to −0.27). Effects could not be ascertained up to 24 months (s.m.d. = −0.18). Similar findings emerged for 50% symptom reduction (relative risk = 1.27–2.79), reliable improvement (relative risk = 1.38–3.17), deterioration (relative risk = 0.67–0.54) and close-to-symptom-free status (relative risk = 1.41–2.80). Among participant-level moderators, only initial depression and anxiety severity were highly credible (P > 0.99). Predicted treatment benefits decreased with lower symptom severity but remained minimally important even for very mild symptoms (s.m.d. = −0.33 for PHQ-9 = 5).
Conclusions
Psychological intervention reduces the symptom burden in individuals with subthreshold depression up to 1 year, and protects against symptom deterioration. Benefits up to 2 years are less certain. We find strong support for intervention in subthreshold depression, particularly with PHQ-9 scores ≥ 10. For very mild symptoms, scalable treatments could be an attractive option.
Using the dual-pathway framework (Beach et al., 2022a), we tested a Neuro-immune Network (NIN) hypothesis: i.e., that chronically elevated inflammatory processes may have delayed (i.e., incubation) effects on young adult substance use, leading to negative health outcomes. In a sample of 449 participants in the Family and Community Health Study who were followed from age 10 to age 29, we examined a non-self-report index of young adult elevated alcohol consumption (EAC). By controlling self-reported substance use at the transition to adulthood, we were able to isolate a significant delayed (incubation) effect from childhood exposure to danger to EAC (β = −.157, p = .006), which contributed to significantly worse aging outomes. Indirect effects from danger to aging outcomes via EAC were: GrimAge (IE = .010, [.002, .024]), Cardiac Risk (IE = −.004, [−.011, −.001]), DunedinPACE (IE = .002, [.000, .008]). In exploratory analyses we examined potential sex differences in effects, showing slightly stronger incubation effects for men and slightly stronger effects of EAC on aging outcomes for women. Results support the NIN hypothesis that incubation of immune pathway effects contributes to elevated alcohol consumption in young adulthood, resulting in accelerated aging and elevated cardiac risk outcomes via health behavior.
Psychological and existential distress is prevalent among patients with life-threatening cancer, significantly impacting their quality of life. Psilocybin-assisted therapy has shown promise in alleviating these symptoms. This systematic review aims to synthesize the evidence on the efficacy and safety of psilocybin in reducing cancer-related distress.
Methods
We searched MEDLINE, APA PsycINFO, Cochrane database, Embase, and Scopus from inception to February 8, 2024, for randomized controlled trials (RCTs), open-label trials, qualitative studies, and single case reports that evaluated psilocybin for cancer-related distress. Data were extracted on study characteristics, participant demographics, psilocybin and psychotherapy intervention, outcome measures, and results. Two authors independently screened, selected, and extracted data from the studies. Cochrane Risk of Bias for RCTs and Methodological Index for Non-Randomized Studies criteria were used to evaluate study quality. This study was registered with PROSPERO (CRD42024511692).
Results
Fourteen studies met the inclusion criteria, comprising three RCTs, five open-label trials, five qualitative studies, and one single case report. Psilocybin therapy consistently showed significant reductions in depression, anxiety, and existential distress, with improvements sustained over several months. Adverse effects were generally mild and transient.
Significance of results
This systematic review highlights the potential of psilocybin-assisted therapy as an effective treatment for reducing psychological and existential distress in cancer patients. Despite promising findings, further large-scale, well-designed RCTs are needed to confirm these results and address existing research gaps.
Objectives/Goals: People with insulin-treated diabetes face hypoglycemia risk due to imperfect insulin replacement and impaired counterregulation. We identified the dopamine antagonist, metoclopramide, as a potential treatment. Hypothesis: Treatment with metoclopramide will prevent the development of impaired counterregulatory response to hypoglycemia. Methods/Study Population: In a pre-clinical model, diabetes was induced in 10-week-old Sprague-Dawley rats with streptozotocin (STZ, 65 mg/kg IP). Rats were divided into three groups: 1) diabetic controls (STZ+RS, n = 6), 2) recurrent hypoglycemia (STZ+RH, n = 7), and 3) recurrent hypoglycemia + metoclopramide (STZ+RH+MET, 3 mg/kg IP, n = 7). After 3 days, all rats underwent a hyperinsulinemic (50 mU/kg/min) and hypoglycemic (~45 mg/dl) clamp. In the clinical trial, adults with Type 1 diabetes (age 20–60, ≥5 years duration) were enrolled in a phase II, double-blinded, placebo-controlled trial. Awareness status was assessed via Gold score, and subjects maintained drug regimens and underwent two hyperinsulinemic-hypoglycemic clamps (where blood glucose was lowered to 100, 65, 55, and 45 mg/dl) to assess counterregulation. Results/Anticipated Results: In the pre-clinical model, glucose infusion rates (GIR) to maintain hypoglycemia were higher in STZ+RH (27±0.9 mg/kg/min) than STZ+RS (19±0.8 mg/kg/min, p Discussion/Significance of Impact: Metoclopramide improves glucoregulatory, sympathoadrenal, and counterregulatory responses to hypoglycemia in pre-clinical models, suggesting dopaminergic regulation. While clinical data are still blinded, increased epinephrine and growth hormone responses suggest treatment may preserve or restore counterregulation.
Poison pills are among the most powerful antitakeover provisions, but studying their economic impact is challenging because of the obvious endogeneity concerns. We address the problem by studying U.S. states’ staggered adoption of poison pill laws (PPLs), which strengthen the right to adopt a pill (i.e., the shadow pill) and increase the validity of visible pills. We document that PPLs make visible pill policy aligned with economic incentives, increasing pill adoption among firms with a high likelihood of takeover, but decreasing it among firms with low takeover likelihood. We also document that PPLs positively impact firm value, especially for innovative firms with more intangible assets.
Findings from contemporary clinical trials suggest that psychedelics are generally safe and may be effective in the treatment of various psychiatric disorders. However, less is known about the risks associated with psychedelic use outside of medically supervised contexts, particularly in populations that are typically excluded from participation in clinical trials.
Methods
Using a preregistered longitudinal observational research design with a purposive sample of US residents between 18 and 50 years old (N=21,990), we investigated associations between self-reported naturalistic psychedelic use and psychotic and manic symptoms, with emphasis on those with psychiatric histories of schizophrenia or bipolar I disorder.
Results
The follow-up survey was completed by 12,345 participants (56% retention), with 505 participants reporting psychedelic use during the 2-month study period. In covariate-adjusted regression models, psychedelic use during the study period was associated with increases in the severity of psychotic and manic symptoms. However, such increases were only observed for those who reported psychedelic use in an illegal context. While increases in the severity of psychotic symptoms appeared to depend on the frequency of use and the intensity of challenging psychedelic experiences, increases in the severity of manic symptoms appeared to be moderated by a personal history of schizophrenia or bipolar I disorder and the subjective experience of insight during a psychedelic experience.
Conclusions
The findings suggest that naturalistic psychedelic use specifically in illegal contexts may lead to increases in the severity of psychotic and manic symptoms. Such increases may depend on the frequency of use, the acute subjective psychedelic experience, and psychiatric history.
This Element explores the idea of publication in media used before, alongside, and after print. It contrasts multiple traditions of unprinted communication in their diversity and particularity. This decentres print as the means for understanding publication; instead, publication is seen as an heuristic term which identifies activities these traditions share, but which also differ in ways not reducible to comparisons with printing. The Element engages with texts written on papyrus, chiselled in stone, and created digitally; sung, proclaimed, and put on stage; banned, hidden and rediscovered. The authors move between Greek inscriptions and Tibetan edicts, early modern manuscripts and AI-assisted composition, monasteries and courts, constantly questioning the term 'publication' and considering the agency of people publishing and the publics they address. The picture that transpires is that of a colourful variety of contexts of production and dissemination, underlining the value of studying 'unprinted' publication in its own right.
Implementation of video call-based cognitive behavioural therapy (CBT) has increased significantly since the COVID-19 pandemic, enabling more flexible delivery, but less is known about user experience and effectiveness. This systematic review and meta-analysis investigated feasibility, acceptability, and effectiveness of individual video call-based CBT for adults with mild to moderate mental health conditions (Prospero CRD42021291055). Medline, Embase, PsycINFO and Web of Science were searched until 4 September 2023. The Effective Public Health Practice Project Quality Assessment Tool (EPHPP) assessed methodological quality of studies. Meta-analysis was conducted in R. Thirty studies (n=3275), published 2000 to 2022, mainly in the USA (n=22/30, 73%), were included. There were 15 randomised control trials, one controlled clinical trial, and 14 uncontrolled studies. Findings indicated feasibility, acceptability and effectiveness (effect size range 0.02–8.30), especially in post-traumatic stress disorder (PTSD) for military populations. Other studies investigated depression, obsessive-compulsive disorder, panic with agoraphobia, insomnia, and anxiety. Studies indicated that initial challenges with video call-based CBT subsided as therapy progressed and technical difficulties were managed with limited impact on care. EPHPP ratings were strong (n=12/30, 40%), moderate (n=12/30, 40%), and weak (n=6/30, 20%). Meta-analysis on 12 studies indicated that the difference in effectiveness of video call-based CBT and in-person CBT in reducing symptoms was not significant (SMD=0.044; CI=–0.086; 0.174). Video calls could increase access to CBT without diminishing effectiveness. Limitations include high prevalence of PTSD studies, lack of standardised definitions, and limited studies, especially those since the COVID-19 pandemic escalated use of video calls.
Key learning aims
This review assesses feasibility, acceptability, and effectiveness of individual video call-based CBT for adults with mild to moderate common mental health conditions, as defined by the ICD-11.
Secondary aims were to assess if the therapeutic relationship is affected and identify any potential training needs in delivering video call-based CBT.
The adjunct meta-analysis quantitatively explored whether video call-based CBT is as effective as in-person interventions in symptom reduction on primary outcome measures by pooling estimates for studies that compare these treatment conditions.
The primary tool for analysing groups acting on trees is Bass--Serre Theory. It is comprised of two parts: a decomposition result, in which an action is decomposed via a graph of groups, and a construction result, in which graphs of groups are used to build examples of groups acting on trees. The usefulness of the latter for constructing new examples of `large (e.g.~nondiscrete) groups acting on trees is severely limited. There is a pressing need for new examples of such groups as they play an important role in the theory of locally compact groups. An alternative `local-to-global approach to the study of groups acting on trees has recently emerged, inspired by a paper of Marc Burger and Shahar Mozes, based on groups that are `universal with respect to some specified `local action. In recent work, the authors of this survey article have developed a general theory of universal groups of local actions, that behaves, in many respects, like Bass--Serre Theory. We call this the theory of local action diagrams. The theory is powerful enough to completely describe all closed groups of automorphisms of trees that enjoy Tits Independence Property $\propP{}$. This article is an introductory survey of the local-to-global behaviour of groups acting on trees and the theory of local action diagrams. The article contains many ideas for future research projects.
To assess the effectiveness of a 3-question decision-support tool to guide the diagnosis and treatment of urinary tract infections (UTIs) in acute care hospitalized patients as an antibiotic and diagnostic stewardship initiative.
Design:
Retrospective cohort study.
Setting:
Four acute care hospitals within the same health system in Miami, FL.
Patients:
124, admitted from the emergency department and hospitalized adult patients, treated with antibiotics for the indication of a UTI between March and April 2023.
Intervention:
We developed a 3-step clinical decision-support tool (CDST) to evaluate the appropriateness of urine cultures and antibiotic treatment. The tool’s recommendations when deciding to prescribe antibiotics were compared with the actual need for treatment throughout the hospitalization, up to the time of patient discharge.
Results:
Overall, 31% of antibiotics prescribed for UTIs were inappropriate and met the criteria for asymptomatic bacteriuria (ASB) based on the CDST. Prospective implementation of the decision-support tool could potentially reduce antibiotic use by 33.6%, corresponding to 265 days of unnecessary therapy. The sensitivity and specificity of the tool were calculated to be 98.6% and 100%, respectively, indicating high accuracy in identifying the need for antibiotic treatment. Urinalysis alone was insufficient to differentiate between symptomatic UTIs and ASB, with leukocyturia present in 95.3% of UTI cases and 94.6% of ASB cases (P = 0.87).
Conclusions:
Implementing a 3-question CDST may reduce unnecessary laboratory work-up and treatment for ASB improving the diagnostic and antimicrobial stewardship of UTIs.
Archaeological sites in Northwest Africa are rich in human fossils and artefacts providing proxies for behavioural and evolutionary studies. However, these records are difficult to underpin on a precise chronology, which can prevent robust assessments of the drivers of cultural/behavioural transitions. Past investigations have revealed that numerous volcanic ash (tephra) layers are interbedded within the Palaeolithic sequences and likely originate from large volcanic eruptions in the North Atlantic (e.g. the Azores, Canary Islands, Cape Verde). Critically, these ash layers offer a unique opportunity to provide new relative and absolute dating constraints (via tephrochronology) to synchronise key archaeological and palaeoenvironmental records in this region. Here, we provide an overview of the known eruptive histories of the potential source volcanoes capable of widespread ashfall in the region during the last ~300,000 years, and discuss the diagnostic glass compositions essential for robust tephra correlations. To investigate the eruption source parameters and weather patterns required for ash dispersal towards NW Africa, we simulate plausible ashfall distributions using the Ash3D model. This work constitutes the first step in developing a more robust tephrostratigraphic framework for distal ash layers in NW Africa and highlights how tephrochronology may be used to reliably synchronise and date key climatic and cultural transitions during the Palaeolithic.
There is an increasing emphasis worldwide on breeding wheat cultivars with higher biomass and grain yield, whilst reducing excessive input of N fertilizers. Modern plant breeding has narrowed the genetic base of bread wheat, so exploring new sources of genetic variation for leaf photosynthesis traits and biomass to underpin grain yield improvement has become necessary. Our objectives were to quantify the genetic variability in a range of landrace-derived lines and elite bread wheat genotypes in flag-leaf photosynthesis traits, biomass and N-use efficiency for potential application in pre-breeding. Sixteen bread wheat genotypes including elite spring wheat cultivar Paragon × landrace crosses were tested in two field experiments in the UK. Averaging across years, pre-anthesis flag-leaf photosynthesis rate ranged amongst genotypes from 26.0 to 31.5 μmol/m2/s (P < 0.001) and post-anthesis from 14.2 to 18.6 μmol/m2/s (P < 0.001). Two landrace-derived lines had greater post-anthesis flag-leaf photosynthesis rate (P < 0.001) than their elite parent Paragon. There was a trend for a positive correlation among genotypes between post-anthesis flag-leaf photosynthesis rate and biomass (r = 0.47, P = 0.06). Two landrace derivatives showed higher post-anthesis flag-leaf stomatal conductance than Paragon. Our results indicated that introgression of traits from wider germplasm into elite UK modern wheat germplasm offers scope to raise flag-leaf photosynthetic rate and biomass.
Hyperplexed in-situ targeted proteomics via antibody immunodetection (i.e., >15 markers) is changing how we classify cells and tissues. Differently from other high-dimensional single-cell assays (flow cytometry, single-cell RNA sequencing), the human eye is a necessary component in multiple procedural steps: image segmentation, signal thresholding, antibody validation, and iconographic rendering. Established methods complement the human image evaluation, but may carry undisclosed biases in such a new context, therefore we re-evaluate all the steps in hyperplexed proteomics. We found that the human eye can discriminate less than 64 out of 256 gray levels and has limitations in discriminating luminance levels in conventional histology images. Furthermore, only images containing visible signals are selected and eye-guided digital thresholding separates signal from noise. BRAQUE, a hyperplexed proteomic tool, can extract, in a marker-agnostic fashion, granular information from markers which have a very low signal-to-noise ratio and therefore are not visualized by traditional visual rendering. By analyzing a public human lymph node dataset, we also found unpredicted staining results by validated antibodies, which highlight the need to upgrade the definition of antibody specificity in hyperplexed immunostaining. Spatially hyperplexed methods upgrade and supplant traditional image-based analysis of tissue immunostaining, beyond the human eye contribution.
Acute myocarditis leading to severe heart failure in paediatric patients is an uncommon but potentially life-threatening condition. The prompt implant of mechanical circulatory devices such as veno-arterial extra-corporeal membrane oxygenation remains the best treatment option to restore an adequate perfusion and improve patient survival in case of refractory cardiogenic shock cases. While few reports describe the in-hospital course of this dramatic disease, with an in-hospital mortality under veno-arterial extra-corporeal membrane oxygenation support around 30%, our study aims to analyse both short- and long-term outcomes after extra-corporeal membrane oxygenation implant.
The harmful consumption of alcohol is known for how tortuous its management can be in mental health, encouraging introspection of it as a serious problem is perhaps the main key to starting to battle against its damaging influence on the development of a functional and full life.
Objectives
To describe a clinical case showing an unpredictible complication in an alcohol detoxification process.
Methods
54-year-old man, native of Cádiz, widowed for half a decade, without children. He resides with his parents in the family home. Currently unemployed for approximately a year. He has previously worked in the IT sector. As a notable somatic history, we found long-established arterial hypertension and a total hip replacement. He has been under irregular follow-up with a mental health team for anxiety-depressive symptoms in the context of grief. He goes to the emergency service brought by his family to begin the detoxification process in the hospital setting. He acknowledges ethanol consumption since he was widowed, which began when he awakes; quantities that ranged between one or up to three bottles of distilled liquor per day, generally consumption is in the home environment. A little less than a year ago, he began to isolate himself in his room and abandon his self-care, eating increasingly insufficient food intake, refusing to receive professional care to quit the habit, mainly because he did not recognize it as disruptive.
The patient was admitted to hospital with symptoms suggestive of withdrawal, making it extremely difficult to control blood pressure levels. On the third day of admission to the acute care unit, fever peaks, blood pressure levels well below normal parameters, and compromised level of consciousness began to be evident.
Results
Blood tests were performed that, together with the clinical picture, suggested imminent septic shock, so critical care was contacted for transfer and stabilization. A germ of probable urinary etiology sensitive to a broad spectrum of antibiotics was isolated in blood cultures, and the medication of the detoxification process was progressively optimized. Once clinical stability was achieved at all levels, an inpatient cessation resource was managed, which the patient accepted and considered suitable for his complete recovery.
Conclusions
A holistic approach to the alcoholic patient is important, since serious problems of an organic nature often arise. This is why a multidisciplinary intervention is necessary, as well as a holistic approach to care, involving both classic pharmacology and assiduous long-term psychotherapeutic intervention.
Emergency psychiatric care, unplanned hospital admissions, and inpatient health care are the costliest forms of mental health care. According to Statistics Canada (2018), almost 18% (5.3 million) of Canadians reported needing mental health support. However, just above half of this figure (56.2%) have reported their needs were fully met. To further expand capacity and access to mental health care in the province, Nova Scotia Health has launched a novel mental health initiative, the Rapid Access, and Stabilization Program (RASP).
Objectives
This study evaluates the effectiveness and impact of the RASP on high-cost health services utilization (e.g. ED visits, mobile crisis visits, and inpatient treatments) and related costs. It also assesses healthcare partners’ (e.g. healthcare providers, policymakers, community leaders) perceptions and patient experiences and satisfaction with the program and identifies sociodemographic characteristics, psychological conditions, recovery, well-being, and risk measures in the assisted population.
Methods
This is a hypothesis-driven program evaluation study that employs a mixed methods approach. A within-subject comparison will examine health services utilization data from patients attending RASP, one year before and one year after their psychiatry assessment at the program. A controlled between-subject comparison will use historical data from a control population will examine whether possible changes in high-cost health services utilization are associated with the intervention (RASP). The primary analysis involves extracting secondary data from provincial information systems, electronic medical records, and regular self-reported clinical assessments. Additionally, a qualitative sub-study will examine patient experience and satisfaction, and examine health care partners’ impressions.
Results
The results for the primary, secondary, and qualitative outcome measures to be available within 6 months of study completion. We expect that RASP evaluation findings will demonstrate a minimum 10% reduction in high-cost health services utilization and corresponding 10% cost savings, and also a reduction in the wait times for patient consultations with psychiatrists to less than 30 calendar days. In addition, we anticipate that patients, healthcare providers, and healthcare partners would express high levels of satisfaction with the new service.
Conclusions
This study will demonstrate the results of the Mental Health and Addictions Program (MHAP) efforts to provide stepped-care, particularly community-based support, to individuals with mental illnesses. Results will provide new insights into a novel community-based approach to mental health service delivery and contribute to knowledge on how to implement mental health programs across varying contexts.