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Importance Ketamine hydrochloride is increasingly used to treat depression and other psychiatric disorders but can induce schizophrenia-like or psychotomimetic symptoms. Despite this risk, the consistency and magnitude of symptoms induced by ketamine or what factors are associated with these symptoms remain unknown. Objective To conduct a meta-analysis of the psychopathological outcomes associated with ketamine in healthy volunteers and patients with schizophrenia and the experimental factors associated with these outcomes. Data Sources MEDLINE, Embase, and PsychINFO databases were searched for within-participant, placebo-controlled studies reporting symptoms using the Brief Psychiatric Rating Scale (BPRS) or the Positive and Negative Syndrome Scale (PANSS) in response to an acute ketamine challenge in healthy participants or patients with schizophrenia. Study Selection Of 8464 citations retrieved, 36 studies involving healthy participants were included. Inclusion criteria were studies (1) including healthy participants; (2) reporting symptoms occurring in response to acute administration of subanesthetic doses of ketamine (racemic ketamine, s-ketamine, r-ketamine) intravenously; (3) containing a placebo condition with a within-subject, crossover design; (4) measuring total positive or negative symptoms using BPRS or PANSS; and (5) providing data allowing the estimation of the mean difference and deviation between the ketamine and placebo condition. Data Extraction and Synthesis Two independent investigators extracted study-level data for a random-effects meta-analysis. Total, positive, and negative BPRS and PANSS scores were extracted. Subgroup analyses were conducted examining the effects of blinding status, ketamine preparation, infusion method, and time between ketamine and placebo conditions. The Meta-analysis of Observational Studies in Epidemiology (MOOSE) and Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed. Main Outcomes and Measures Standardized mean differences (SMDs) were used as effect sizes for individual studies. Standardized mean differences between ketamine and placebo conditions were calculated for total, positive, and negative BPRS and PANSS scores. Results The overall sample included 725 healthy volunteers (mean [SD] age, 28.3 [3.6] years; 533 [73.6%] male) exposed to the ketamine and placebo conditions. Racemic ketamine or S-ketamine was associated with a statistically significant increase in transient psychopathology in healthy participants for total (SMD = 1.50 [95% CI, 1.23-1.77]; P Conclusions and Relevance This study found that acute ketamine administration was associated with schizophrenia-like or psychotomimetic symptoms with large effect sizes, but there was a greater increase in positive than negative symptoms and when a bolus was used. These findings suggest that bolus doses should be avoided in the therapeutic use of ketamine to minimize the risk of inducing transient positive (psychotic) symptoms.

Clear, accepted definitions of treatment resistance and response are needed so that clinical trials of treatments can be compared, and evidence can be meaningfully interpreted to inform clinical practice. In this chapter, we review the definitions of treatment response and resistance used in clinical trials, highlighting the variability in definitions used across studies, as well as a number of problems with the definitions used, including mixing treatment-intolerant patients with treatment-resistant patients and limited evaluation of the adequacy of treatment in many cases. The chapter then summarizes the work undertaken by the Treatment Response and Resistance in Psychosis working group to produce consensus guidelines and benchmarks to address these issues. Also reviewed are the principles underlying the concept of resistance developed by the working group. Finally, the chapter discusses the implications of these findings for clinical practice.

In the classical worlds of Julius Caesar and Coriolanus Shakespeare finds the conditions in which to isolate and analyze the Christian doctrine of vocation, the idea that individuals are destined to fill a place in the body politic or the congregation of believers. Many of Shakespeare's plays pit character against calling. In the Roman tragedies the tension is especially acute. The principals struggle to discern a call in a world dismembered by revolution to the point that a voice can come from a wound. Repeatedly, civic turmoil is described in terms of creation and apocalypse; vocation, hinted at through plot turns and Pauline phrasing, should span and structure the interim. But both plays present a monolithic title character whose all‐consuming integrity threatens to annihilate the society that produced him. Under the pressure of events, Brutus' identity splits, while his co‐conspirators scramble for parts that suddenly seem too few to go around. Coriolanus despises “the many” and their trades t...

Development of small contractors for the construction industry has been advocated and explored in two different contexts in sub-Saharan Africa. This experience could prove useful in relation to the larger debate. Certainly, investigation of the two strands of small contractor development suggested that lessons could be learned for future small contractor development and employment generation from the experience of large programmes of labour-intensive construction and maintenance of rural roads. In particular, the need for a “programme” approach which would include a linked training programme is strongly identified.

Two major themes of Botswana's Fifth and Sixth Development Plans (1976–1991) have been the creation of employment and rural development. As one means of fulfilling both objectives the Government of Botswana explicitly decided that labour-intensive methods should be used by District Councils to improve and maintain the 11,000 km of non-gazetted roads for which they were responsible. To this end, between 1980 and 1982, a Pilot Project was carried out to examine the potential of labour-intensive methods. In 1982, following its evaluation of the Pilot Project, the Ministry of Local Government and Lands decided that the methods developed during the Pilot Project should be replicated throughout Botswana. As a result District Council Roads Units have been established in all districts of Botswana. Over 2,000 people are employed.

From the late 1950s to the late 1970s the use of industrialised methods of building in the U.K. took place almost entirely in the public sector: local authorities and new towns. Having first established this proposition, the paper continues to describe in quantitative terms: (i) the proportion of all local authority housing built by industrialised methods; (ii) the distribution of industrialised building among regions and local authorities; (iii) the type of dwelling produced in relation to the form of the building, the method of construction and the material used; (iv) the major systems involved, and finally (v) the costs. A summary of the major findings of such a quantitative analysis may be found in the conclusions.

During the 1950s and 1960s policies based on the principles of industrialised building were introduced in many countries. The paper will summarise the data on the extent to which industrialised methods of building were used in the countries of Eastern and Western Europe. The major conclusion from the paper is that the widespread and continued use of industrialised building was directly related to the scale of the public housing sector.