Low Probability Of Success Research Articles

Likelihood of retrograde double-J stenting according to ureteral obstructing pathology

To evaluate the likelihood of retrograde double-J stenting in urgent ureteral drainage according to obstructing pathology. From July 2002 to January 2003, 43 consecutive patients with ureteral obstruction who needed urgent decompression were evaluated at our institution, where we performed a total of 47 procedures. Emergency was defined as ureteral obstruction associated with infection, obstructive acute renal failure, or refractory pain. Ureteral obstruction was defined as intrinsic and extrinsic based on etiology and evaluated by ultrasound. Patients submitted to previous double-J stenting were excluded. Failures in retrograde ureteral stenting were treated with percutaneous nephrostomy. Results were analyzed with Fisher's exact test and regression analysis. Failure in retrograde ureteral stenting occurred in 9% (2/22) and 52% (13/25) of the attempts in patients with intrinsic and extrinsic obstruction respectively (p < 0.001). Failures in stenting extrinsic obstructions occurred due to lack of identification of the ureteral meatus in 77% and impossibility of catheter progression in 23% (p < 0.05). All attempts of retrograde catheter insertion failed in obstructions caused by prostate or bladder pathologies (6/6). Inability to identify the ureteral meatus was the cause of all failures. Retrograde double-J stenting has a low probability of success in extrinsic ureteral obstruction caused by prostate or bladder disease. Such cases might be best managed with percutaneous nephrostomy.

Effectiveness of noncoplanar IMRT planning using a parallelized multiresolution beam angle optimization method for paranasal sinus carcinoma

To determine the effectiveness of noncoplanar beam configurations and the benefit of plans using fewer but optimally placed beams designed by a parallelized multiple-resolution beam angle optimization (PMBAO) approach. The PMBAO approach uses a combination of coplanar and noncoplanar beam configurations for intensity-modulated radiation therapy (IMRT) treatment planning of paranasal sinus cancers. A smaller number of beams (e.g. 3) are first used to explore the solution space to determine the best and worst beam directions. The results of this exploration are then used as a starting point for determining an optimum beam orientation configuration with more beams (e.g. 5). This process is parallelized using a message passing interface, which greatly reduces the overall computation time for routine clinical practice. To test this approach, treatment for 10 patients with paranasal sinus cancer was planned using a total of 5 beams from a pool of 46 possible beam angles. The PMBAO treatment plans were also compared with IMRT plans designed using 9 equally spaced coplanar beams, which is the standard approach in our clinic. Plans with these two different beam configurations were compared with respect to dose conformity, dose heterogeneity, dose-volume histograms, and doses to organs at risk (i.e., eyes, optic nerve, optic chiasm, and brain). The noncoplanar beam configuration was superior in most paranasal sinus carcinoma cases. The target dose homogeneity was better using a PMBAO 5-beam configuration. However, the dose conformity using PMBAO was not improved and was case dependent. Compared with the 9-beam configuration, the PMBAO configuration significantly reduced the mean dose to the eyes and optic nerves and the maximum dose to the contralateral optical path (e.g. the contralateral eye and optic nerve). The maximum dose to the ipsilateral eye and optic nerve was also lower using the PMBAO configuration than using the 9-beam configuration, although this difference was not significant. The mean doses to the optic chiasm and brain are marginally lower using the PMBAO configuration than using 9-beam configuration. The maximum doses to the optic chiasm and brain are the same with the PMBAO configuration and the 9-beam configuration. Parallelized multiple-resolution beam angle optimization with an optimized noncoplanar beam configuration is an effective and practical approach for IMRT treatment planning. Five-beam treatment plans optimized using the PMBAO are at least equivalent to, and overall better than, the plans using 9 equally spaced coplanar beams.

Optical implementation of quantum computers

Optical quantum computation was limited to a few photon applications such as quantum cryptography and partial teleportation until 2001. Then the possibility of performing arbitrary logic conditional on certain detection outcomes was introduced by Knill, Laflamme and Milburn (Nature 2001 409 46). Simple circuits consisting of single photon sources, entangled pair sources, linear optical elements and high efficiency photon counting detectors can be used to develop probabilistic two-photon logic gates. Initially such gates show a low probability of success but can approach the success rate of deterministic (non-linear) logic at the cost of added complexity. These developments have led to the emergence of a novel field of research aimed at improving the efficiency of linear logic and developing the efficient sources and detectors for its implementation. This topical issue of Journal of Optics B: Quantum and Semiclassical Optics is devoted to recent advances in this field.

Wind-dispersed Seed Deposition Patterns and Seedling Recruitment of Artemisia halodendron in a Moving Sandy Land

Artemisia halodendron is a native sub-shrub that occurs mainly in moving and semi-fixed sandy lands in Inner Mongolia, China. Information on the spatial patterns of wind-dispersed seed deposition and seedling recruitment of A. halodendron inhabiting moving sandy lands is very limited. The aim of this study was to examine wind-dispersed seed deposition patterns and post-dispersal recruitment of A. halodendron seedlings. * The spatial patterns of wind-dispersed seed deposition and seedling recruitment of A. halodendron were examined by investigating the numbers of deposited seeds, emerged and surviving seedlings using sampling points at a range of distances from the parent plant in eight compass directions for two consecutive growing seasons. * Wind-dispersed seed deposition showed considerable variation between directions and years. Wind transported A. halodendron seeds only a few meters away from the parent plant in all eight directions. Seedling emergence and establishment also showed between-direction and between-year variability, but the spatial pattern of seedling distribution differed from that of seed deposition. Only a very small fraction (<1 %) of the deposited seeds emerged in the field and survived for long enough to be included in our seedling censuses at the end of the growing season. * The spatial variation in wind speed and frequency strongly affects the pattern of seed deposition, although the variation in seed deposition does not determine the spatial pattern of seedling recruitment. Seeds of A. halodendron are not dispersed very well by wind. The low probability of recruitment success for A. halodendron seedlings suggests that this species does not rely on seedling recruitment for its persistence and maintenance of population.

Ownership vs. Contract: How Vertical Integration Affects Investment Decisions in Pharmaceutical R&amp;D

This paper explores the efiect of vertical integration on investment behavior in the pharmaceutical industry. I study a detailed, project-level sample of 4057 drug candidates that were sponsored by 40 large pharmaceutical flrms during the period 1984-2001. Of these projects, 447 were conducted through a contractual alliance with another, smaller company that had discovered the drug candidate. The existence of these two types of governance structures allows me to compare integrated and non-integrated projects within the same flrm. Controlling for project and flrm characteristics, I document that pharmaceutical flrms are more selective in continuing their integrated projects than in continuing projects governed by contract. I hypothesize that this difierence is caused by the rigidity of the contract that governs non-integrated projects, making them less ∞exible in adapting to changes in the flrm’s situation. In line with this hypothesis, I document that although more frequently continued, non-integrated projects have a lower probability of success. Moreover, investment in non-integrated projects is less sensitive to the flrm’s cash ∞ow and to the existence of other projects in the flrm.

Urban domestic gardens (II): experimental tests of methods for increasing biodiversity

The extent and continued expansion of urbanisation has focused attention on the significance for native biodiversity of those green spaces remaining within such areas and the most appropriate methods of managing them. In the UK, a high proportion of urban space is comprised of the private or domestic gardens associated with residential dwellings, and many recommendations have been made for simple changes to improve their value for biodiversity (‘wildlife gardening’). Here, we report the results of replicated experimental tests of five such common recommendations, involving the introduction to gardens of (i) artificial nest sites for solitary bees and wasps; (ii) artificial nest sites for bumblebees; (iii) small ponds; (iv) dead wood for fungi and other saproxylic organisms; and (v) patches of nettles Urtica dioica L. for butterfly larvae. The broad conclusion is that whilst some methods for increasing the biodiversity of garden environments may be very effective, others have a low probability of success on the timescales and spatial scales likely to be acceptable to many garden owners. If one of the functions of small scale biodiversity enhancement is to develop and encourage awareness of biodiversity and its conservation, then encouragement to conduct particular activities must be balanced with a realistic appraisal of their likely success.

Predicting release success of captive-reared loggerhead shrikes (Lanius ludovicianus) using pre-release behavior

We assessed whether behavioral markers could be used to evaluate pair compatibility and predict pair bond success of captive-reared San Clemente loggerhead shrikes (Lanius ludovicianus mearnsi) released into the wild. Potential breeding pairs of shrikes were introduced at the Zoological Society of San Diego's captive-breeding facility and then moved to release cages located in suitable but unoccupied habitat. Courting pairs were affected negatively by the disturbance of translocation to a new location and generally needed a few days to reinitiate pair bonding in the release enclosures. We separated and returned pairs to captivity when intra-pair aggression or cessation of all courtship behavior occurred; all other pairs were released into the wild. The rate of nest approaches was the best marker to predict a successful release into the wild (i.e., pairs that remained near the release site and attempted to breed). Additionally, all experienced breeding pairs (i.e., pairs with males and females with prior captive breeding experience) exhibiting nesting behavior were successful, although previous experience alone does not ensure post-release breeding. Results from this study indicate the importance of assessing behaviors of individuals paired for population augmentation. In using behavioral cues, identifying pairs with a low probability of success is possible, and replacing these pairs with individuals that have a higher likelihood of post-release success can occur. This strategy will be important to efficiently restore imperiled populations of endangered species while working within temporal and financial constraints. Zoo Biol 0:1–12, 2005. © 2005 Wiley-Liss, Inc.

Discontinuation of pegylated interferon plus ribavirin in patients who are not responding to therapy – patients’ views of early cessation of therapy

Current therapy for chronic hepatitis C infection involves a course of pegylated interferon and ribavirin. Patients who do not show a virological response after 12 weeks of therapy have a low probability of sustained virological response and it is therefore recommended that such patients stop treatment. To assess patients' views of early treatment cessation. We conducted a open-labelled study in three UK centres, in which patients with biopsy-proven chronic hepatitis C requiring therapy were offered the choice of a full course of therapy with 40 kDa pegylated interferon-alpha 2a plus ribavirin (24 or 48 weeks depending on viral genotype) or early cessation if therapy had failed after 12 weeks. Ninety-five participants were enrolled and the majority (69%) did not wish to discontinue therapy even if it had low probability of success. In this unselected UK population, very few patients (4%) did not achieve an early virological response with the 40-kDa pegylated interferon-alpha 2a plus ribavirin and two of the four early virological non-responders decided to continue therapy. Early discontinuation of 'ineffective' anti-viral therapy may prove less popular with patients than with health care providers, and further patient-directed education regarding the cost-effectiveness of therapy will be needed if early discontinuation of unsuccessful therapy is to be accepted by patients.

A Model of Entrepreneurial Finance

We analyze how optimal contracting between an entrepreneur and a financial institution depends on the cash flow characteristics of the entrepreneur's firm. Because the entrepreneur prefers continuing the firm over liquidating it, and aggressive continuation strategies over conservative strategies, the institution must monitor the firm and exercise some control over its decisions. The institution's own liquidity concerns make it prefer less exposure to the firm's risk, all else equal. For firms with limited financial slack, the optimal contract resembles convertible debt only if the institution monitors more actively; otherwise, the optimal contract is debt. Convertible debt and active monitoring (venture capital finance) are optimal only when the following conditions are met: (1) the aggressive continuation strategy is not too profitable on average, ex-ante; (2) the firm faces high uncertainty in its choice of continuation strategy; and (3) the firm's cash flow distribution is highly skewed, with low probability of success, low liquidation value, and high returns if successful. If these conditions are not met, debt and passive monitoring (bank finance) are optimal. These results mirror entrepreneurial firms' actual choice between bank finance and venture capital finance. For firms with somewhat higher financial slack and high strategic uncertainty, a third option may be optimal: convertible debt with passive monitoring by the institution. This resembles the circumstances and structure of so called mezzanine finance.

Managing a Portfolio of Interdependent New Product Candidates in the Pharmaceutical Industry

Highly regulated industries such as pharmaceuticals and agrochemicals face the challenge of maintaining a 0continuous stream of new products. This is difficult because of low probabilities of technical success, high development costs, uncertain market impact, a scarcity of good new product ideas, and limited human and capital resources available to develop them. The problem of evaluating and selecting which new products to develop and then of sequencing or of scheduling them is complicated further by the presence of dependencies between products both in the market place and in the development process itself.This study proposes a portfolio management approach that selects a sequence of projects, which maximizes the expected economic returns at an acceptable level of risk for a given level of resources in a new product development pipeline. A probabilistic network model of distinct activities is used to capture all the activities and resources required in the “process” of developing a new drug. A prioritization scheme suggesting sequences for developing new independent drug candidates with unlimited resources is generated with a conventional bubble chart approach. These sequences initiate a genetic algorithm (GA)‐based search for the optimal sequence in the presence of product dependencies and limited resources. By statistically evaluating the sequences generated during the GA search using a discrete event simulation model, it is possible to construct an economic reward‐risk frontier that illustrates the trade‐offs between expected rewards and risks. The model ideally is suited to answer various “what if” questions relative to changes in the resource level on pipeline performance.The methodology is illustrated with an industrially motivated case study, involving nine interdependent new product candidates targeting three diseases. The dramatic results yield a candidate sequence with an expected return 28 percent higher than the sequence suggested by the bubble chart approach at almost the same level of risk. The synergism among the candidate dependencies, pipeline resources, and economic and technical uncertainties demonstrates the necessity of a computationally intensive approach if the best development strategy is to be realized.

Options for Managing Invasive Marine Species

Marine biological invasions are increasingly recognised as a threat to biodiversity and coastal industry, including fisheries. Globally, efforts are underway to contain, if not eradicate, several high-impact marine invasive species. However, working in a marine environment places unique social, political and technical constraints on options for pest control, which we explored in a series of stakeholder workshops. Results suggest that current efforts are low risk and publicly acceptable, but have a low probability of success against established invaders. However, techniques deemed likely to be successful and ultimately needed in a marine context are currently more contentious for social and political reasons. To control introduced marine pests, scientists and managers will need to overcome perceptual biases among marine stakeholders, develop a decision-making framework for what is perceived to be an open system, and focus on technologies likely to be both effective and publicly and politically acceptable.

On the detectability of intelligent civilizations in the galaxy

In this paper we argue for the possibility that even in the event of a Galaxy teeming with extraterrestrial intelligence (ETI) the probability of receiving recognizable signals from the ETIs may be very low. There are two majors factors that may limit our ability to detect other civilizations. (i) Evolutionary mismatches may cause difficulties analogous to humans attempting to communicate with lower primates. (ii) Independent evolutionary paths resulting from differing planetary/stellar environments may result in life whose cognitive processes and consequent perceptions of the universe are very different from ours. Interpreting signals from such civilizations may prove a very difficult or even futile task. Even on Earth, an example of a cognitive mismatch is that between humans and dolphins, where evolution in very different environments has led to difficulty in establishing communication between these two species. The main effect of the second factor is to limit communication while the effect of the first is to constrain what communication is possible to a "window of opportunity", a finite period of time, ??, when communication may be possible before diverging evolution makes it impossible. For example, if the number of ETIs in the Galaxy is one million and if ?? &lt; 10 6 years, the average separation of "contactable" civilizations, (r) &gt; 5 ? 10 3 light years so that one star in 10 10 harbors such a civilization. If the above arguments are correct we reach the following conclusions. The absence of detected signals does not translate into an absence of ETI?s. Targeting individual stars in the search for ETI has a low probability of success. The use of radio signals is of limited value because with such large separations between "contactable" civilizations interstellar scintillation strongly limits the propagation of radio signals. Similarly, optical communication would be hindered by interstellar extinction. Possible alternatives to current searches for narrow band signals include listening for modulated broadband signals searching for narrow-band signals in the microwave/FIR spectrum and searching for evidence of artificially processed environments. All such searches would need to be "all sky" to have a reasonable chance of success.

Skill Signaling, Prospect Theory, and Regret Theory

Failure is embarrassing. In gambles involving both skill and chance, we show that a strategic desire to avoid appearing unskilled generates behavioral anomalies that are typically explained by prospect theory's concepts of loss aversion, probability weighting, and framing effects. Loss aversion arises because losing any gamble, even a friendly bet with little or no money at stake, reflects poorly on the decision maker's skill. Probability weighting emerges because winning a gamble with a low probability of success is a strong signal of skill, while losing a gamble with a high probability of success is a strong signal of incompetence. Framing matters when there are multiple equilibria and the framing of a gamble affects beliefs, e.g., when someone takes a dare rather than admit a lack of skill. The analysis is based on models from the career concerns literature and is closely related to early social psychology models of risk taking. The results provide an alternative perspective on the existence of prospect theory behavior in managerial and financial decisions where both skill and chance are important. We identify specific situations where skill signaling makes opposite predictions than prospect theory, allowing for tests between the strategic and behavioral approaches to understanding risk.

Taxes and Non-Renewable Resources: The Impact on Exploration and Development

Oil & gas projects consist of a series of options. The mineral owner must first decide whether to spend money on in order to learn the extent of potential reserves, the cost and timing of recovering the reserves, and the probability that the reserves are actually recoverable. The mineral owner holds an since the owner need not explore immediately but may wait until an increase in mineral makes the potential rewards from exploration more promising. After exploration of a property, the owner holds a The owner may pay to drill a test well to see if the reserves are recoverable, or the owner may put off any such test until are higher. If the test well proves there are recoverable reserves, the owner has a This option consists of the ability to complete the test well as a producer, and to drill and complete any other wells required to completely drain the recoverable reserves. The incentives for exploration, development, and production depend on the prices at which an investor will execute each option. This article examines the impact of various tax policies on exploration and development threshold prices, using a simplified production model that collapses the production option into the development option. Capitalizing rather than expensing development costs (such as intangible drilling costs) creates incentives to do projects that have a lower probability of success, that have shorter well lives, and that have lower development costs. This shift in incentives creates a nonneutrality, causing investors to develop some properties prematurely while unduly delaying the development of other projects. Capitalizing development costs also causes a slight increase in the exploration threshold price and therefore reduces exploration. Capitalizing rather than expensing exploration costs (such as the costs of seismic analysis to detect potential underground deposits) results in a more complicated pattern of effects. This policy causes a large increase in the exploration threshold price, thereby reducing exploration. Since the taxpayer will not recover capitalized exploration costs until development, this policy also reduces the cost of development and lowers development threshold prices. As a consequence, capitalizing exploration costs results in more intensive development and production of known reserves as well as reduced exploration. This pattern is undesirable if the goal is to enhance national security by encouraging the creation of a pool of reserves that are available for immediate exploitation in case foreign supplies become unavailable. It also is possible that taxpayers may be able to circumvent most of the impact of rules requiring capitalization of exploration costs by strategically realizing losses. This possibility may blunt the undesirable national security impact of such rules, but the costs of the associated trading are social costs that would not arise under expensing.

Prediction of human pharmacokinetics based on preclinical in vitro and in vivo data.

During the drug discovery process, candidate compounds are screened for their main drug metabolism and pharmacokinetic (DMPK) properties (absorption, distribution, metabolic stability, excretion) to assess their potential to become new drug products. Prentis observed that, of 247 new chemical entities which were withdrawn from drug development before 1985, 198 (80%) failed because of inappropriate pharmacokinetics (Prentis et al. 1988). Kennedy confirmed this conclusion in 1997 by reporting that, apart from a lack of efficacy, poor pharmacokinetic properties were still the main reason for terminating the development of drug candidates (Kennedy 1997). Nowadays, the drop out rate because of pharmacokinetic reasons has probably decreased because DMPK issues are being considered in the discovery process. Therefore, approaches to predict human pharmacokinetic profiles are highly desirable to help select the best candidates for development and/or to reject those with a low probability of success. This can drastically reduce the time and expense of drug development (Norris et al. 2000). Since drug discovery has to screen a large number of compounds, the methods used must be capable of predicting the human pharmacokinetics from a limited set of input data.

High predictability in introduction outcomes and the geographical range size of introduced Australian birds: a role for climate

Summary We investigated factors hypothesized to influence introduction success and subsequent geographical range size in 52 species of bird that have been introduced to mainland Australia. The 19 successful species had been introduced more times, at more sites and in greater overall numbers. Relative to failed species, successfully introduced species also had a greater area of climatically suitable habitat available in Australia, a larger overseas range size and were more likely to have been introduced successfully outside Australia. After controlling for phylogeny these relationships held, except that with overseas range size and, in addition, larger‐bodied species had a higher probability of introduction success. There was also a marked taxonomic bias: gamebirds had a much lower probability of success than other species. A model including five of these variables explained perfectly the patterns in introduction success across‐species. Of the successful species, those with larger geographical ranges in Australia had a greater area of climatically suitable habitat, traits associated with a faster population growth rate (small body size, short incubation period and more broods per season) and a larger overseas range size. The relationships between range size in Australia, the extent of climatically suitable habitat and overseas range size held after controlling for phylogeny. We discuss the probable causes underlying these relationships and why, in retrospect, the outcome of bird introductions to Australia are highly predictable.

Sequential parimutuel games

In a parimutuel betting system, a successful player’s return depends on the number of other players who choose the same action. This paper examines a general solution for two-action sequential parimutuel games, and shows how the (unique) equilibrium of such games leads to a simple pattern of behavior. In particular, we show that there is an advantage to being an early mover, that early players might choose actions with an ex ante low probability of success, and that player action choices can ‘flip’ with small changes in the parameters of the game.

Long-term correlations in the spike trains of medullary sympathetic neurons.

Fano factor analysis was used to characterize the spike trains of single medullary neurons with sympathetic nerve-related activity in cats that were decerebrate or anesthetized with Dial-urethan or urethan. For this purpose, values (Fano factor) of the variance of the number of extracellularly recorded spikes divided by the mean number of spikes were calculated for window sizes of systematically varied length. For window sizes < or =10 ms, the Fano factor was close to one, as expected for a Bernoulli process with a low probability of success. The Fano factor dipped below one as the window size approached the shortest interspike interval (ISI) and reached its nadir at window sizes near the modal ISI. The extent of the dip reflected the shape (skewness) of the ISI histogram with the dip being smallest for the most asymmetric distributions. Most importantly, for a wide range of window sizes exceeding the modal ISI, the Fano factor curve took the form of a power law function. This was the case independent of the component (cardiac related, 10 Hz, or 2--6 Hz) of inferior cardiac sympathetic nerve discharge to which unit activity was correlated or the medullary region (lateral tegmental field, raphe, caudal and rostral ventrolateral medulla) in which the neuron was located. The power law relationship in the Fano factor curves was eliminated by randomly shuffling the ISIs even though the distribution of the intervals was unchanged. Thus the power law relationship arose from long-term correlations among ISIs that were disrupted by shuffling the data. The presence of long-term correlations across different time scales reflects the property of statistical self-similarity that is characteristic of fractal processes. In most cases, we found that mean ISI and variance for individual spike trains increased as a function of the number of intervals counted. This can be attributed to the clustering of long and short ISIs, which also is an inherent property of fractal time series. We conclude that the spike trains of brain stem sympathetic neurons have fractal properties.

ON THE SCALABILITY OF ON-DEMAND ROUTING PROTOCOLS FOR MOBILE AD HOC NETWORKS: AN ANALYTICAL STUDY

Wireless systems, and mobile ad hoc networks in particular, are more likely to experience transmission and routing errors than their wired counterpart. Factors like the lack of infrastructure, node mobility, and random radio link quality can contribute to significantly higher error rates in these networks. In addition, errors have a more serious impact on the network's resources, due to limitations in bandwidth and battery power inherent to the wireless ad hoc environment. This further complicates the task of designing scalable routing protocols, since larger networks are likely to experience even more errors, which may lead to slower convergence, longer end-to-end delay and unnacceptably high number of retransmissions. In this paper, we focus on the impact of error prevention and recovery on the scaling properties of on-demand protocols for ad hoc networks. Our analytical study, based on the evaluation of the Witness Aided Routing (WAR) and the Dynamic Source Routing (DSR) protocols, shows that the lack of localized intervention in handling errors translates eventually into lack of scalability, both in terms of performance and resource consumption. As route length increases, the performance of DSR degrades dramatically, especially in the presence of fluctuating wireless link quality. Even for small routes, DSR's lack of an error handling mechanism leads to very low probability of success when there is a non-zero probability that links are not bidirectional. On the other hand, WAR remains relatively insensitive both to the length of the route and to variations in mobility and call rates, and has a higher tolerance to radio link instability. This indicates that lacalized error correction can increase route effectiveness and alleviate the effects of short-lived radio link problems to an extent that allows the protocol to scale with the network size.

The prevention of schizophrenia: what interventions are safe and effective?

Obstetric complications appear to increase the risk of developing schizophrenia, and post-World War II improvements in obstetric care may have contributed to a decline in the incidence of the illness in the developed world. Educating providers and consumers of psychiatric and obstetric services about the risk of obstetric complications in increasing the risk of schizophrenia could bring about a further small decrease in the incidence of the illness, safely and at low cost. On the other hand, attempts to prevent the occurrence of schizophrenia by treating people who manifest high-risk indicators prior to the development of the illness have a low probability of success and a high probability of unintended negative consequences. Early intervention with people who have developed the full schizophrenia syndrome is likely to have few negative effects and may yield benefits, although it is not yet clear that it will.