Reservoir host immunology and life history shape virulence evolution in zoonotic viruses.

The management of future pandemic risk requires a better understanding of the mechanisms that determine the virulence of emerging zoonotic viruses. Meta-analyses suggest that the virulence of emerging zoonoses is correlated with but not completely predictable from reservoir host phylogeny, indicating that specific characteristics of reservoir host immunology and life history may drive the evolution of viral traits responsible for cross-species virulence. In particular, bats host viruses that cause higher case fatality rates upon spillover to humans than those derived from any other mammal, a phenomenon that cannot be explained by phylogenetic distance alone. In order to disentangle the fundamental drivers of these patterns, we develop a nested modeling framework that highlights mechanisms that underpin the evolution of viral traits in reservoir hosts that cause virulence following cross-species emergence. We apply this framework to generate virulence predictions for viral zoonoses derived from diverse mammalian reservoirs, recapturing trends in virus-induced human mortality rates reported in the literature. Notably, our work offers a mechanistic hypothesis to explain the extreme virulence of bat-borne zoonoses and, more generally, demonstrates how key differences in reservoir host longevity, viral tolerance, and constitutive immunity impact the evolution of viral traits that cause virulence following spillover to humans. Our theoretical framework offers a series of testable questions and predictions designed to stimulate future work comparing cross-species virulence evolution in zoonotic viruses derived from diverse mammalian hosts.

Bats host the most virulent-but not the most dangerous-zoonotic viruses.

SignificanceThe clear need to mitigate zoonotic risk has fueled increased viral discovery in specific reservoir host taxa. We show that a combination of viral and reservoir traits can predict zoonotic virus virulence and transmissibility in humans, supporting the hypothesis that bats harbor exceptionally virulent zoonoses. However, pandemic prevention requires thinking beyond zoonotic capacity, virulence, and transmissibility to consider collective "burden" on human health. For this, viral discovery targeting specific reservoirs may be inefficient as death burden correlates with viral, not reservoir, traits, and depends on context-specific epidemiological dynamics across and beyond the human-animal interface. These findings suggest that longitudinal studies of viral dynamics in reservoir and spillover host populations may offer the most effective strategy for mitigating zoonotic risk.

A Pilot Trial of a Health Promotion and Illness Prevention Paradigm in the Perinatal Period.

OBJECTIVES: This is a pilot study of the Vermont Family Based Approach, an innovative health promotion program designed to address behavioral health prevention in primary care, adapted for perinatal women. We aimed to determine the acceptability of the intervention across socioeconomic strata, and to identify if participation improves perinatal mental health. METHODS: Recruitment occurred at a general obstetrics practice. Women 12-25 weeks gestation were paired with a wellness coach who administered a wellness assessment and used motivational interviewing to facilitate individualized plans based on evidence-based domains of health promotion. Participants were offered access to free, co-located wellness activities through the peripartum, and referred to behavioral health services if appropriate. RESULTS: 93 women consented; 16 Medicaid Insured women (MI) and 30 Privately Insured (PI) were randomized to the intervention. Of all activities, yoga and parenting activities were most appealing, with 58% of women attending. PI (M = 12.30, SD = 11.71) attended significantly more activities than MI (M = 3.81, SD = 12.30; p = .001). Trauma exposure was inversely associated with attendance (p = .004). Randomization to the intervention was not associated with improvements in internalizing symptoms or perceived stress at 12 months postpartum, however, attending three or more wellness activities was associated with a decrease in perceived stress between baseline and 12 months postpartum. CONCLUSION: This program appeared acceptable and engaging to women with private insurance, but less so with Medicaid. The trial failed to demonstrate improvement in internalizing scores, but of those randomized to the intervention, higher engagement was associated with decreased stress one year after giving birth.

Optimising predictive models to prioritise viral discovery in zoonotic reservoirs.

Despite the global investment in One Health disease surveillance, it remains difficult and costly to identify and monitor the wildlife reservoirs of novel zoonotic viruses. Statistical models can guide sampling target prioritisation, but the predictions from any given model might be highly uncertain; moreover, systematic model validation is rare, and the drivers of model performance are consequently under-documented. Here, we use the bat hosts of betacoronaviruses as a case study for the data-driven process of comparing and validating predictive models of probable reservoir hosts. In early 2020, we generated an ensemble of eight statistical models that predicted host-virus associations and developed priority sampling recommendations for potential bat reservoirs of betacoronaviruses and bridge hosts for SARS-CoV-2. During a time frame of more than a year, we tracked the discovery of 47 new bat hosts of betacoronaviruses, validated the initial predictions, and dynamically updated our analytical pipeline. We found that ecological trait-based models performed well at predicting these novel hosts, whereas network methods consistently performed approximately as well or worse than expected at random. These findings illustrate the importance of ensemble modelling as a buffer against mixed-model quality and highlight the value of including host ecology in predictive models. Our revised models showed an improved performance compared with the initial ensemble, and predicted more than 400 bat species globally that could be undetected betacoronavirus hosts. We show, through systematic validation, that machine learning models can help to optimise wildlife sampling for undiscovered viruses and illustrates how such approaches are best implemented through a dynamic process of prediction, data collection, validation, and updating.

Reproduction, seasonal morphology, and juvenile growth in three Malagasy fruit bats.

The island nation of Madagascar is home to three endemic species of Old World fruit bat in the family Pteropodidae: Pteropus rufus, Eidolon dupreanum, and Rousettus madagascariensis, all three of which are IUCN Red Listed under some category of threat. Delineation of seasonal limits in the reproductive calendar for threatened mammals can inform conservation efforts by clarifying parameters used in population viability models, as well as elucidate understanding of the mechanisms underpinning pathogen persistence in host populations. Here, we define the seasonal limits of a staggered annual birth pulse across the three species of endemic Madagascar fruit bat, known reservoirs for viruses of high zoonotic potential. Our field studies indicate that this annual birth pulse takes place in September/October for P. rufus, November for E. dupreanum, and December for R. madagascariensis in central-eastern Madagascar where the bulk of our research was concentrated. Juvenile development periods vary across the three Malagasy pteropodids, resulting in near-synchronous weaning of pups for all species in late January-February at the height of the fruiting season for this region. We here document the size range in morphological traits for the three Malagasy fruit bat species, with P. rufus and E. dupreanum among the larger of pteropodids globally and R. madagascariensis among the smaller. All three species demonstrate subtle sexual dimorphism with males being larger than females. We explore seasonal variation in adult body condition by comparing observed body mass with body mass predicted by forearm length, demonstrating that pregnant females add weight during staggered gestation periods and males lose weight during the nutritionally deficit Malagasy winter. Finally, we quantify forearm, tibia, and ear length growth rates in juvenile bats, demonstrating both faster growth and more protracted development times for P. rufus as compared with E. dupreanum and R. madagascariensis. The longer development period for the already-threatened P. rufus further undermines the conservation status of this species as human hunting is particularly detrimental to population viability during reproductive periods. Our work highlights the importance of longitudinal field studies in collecting critical data for mammalian conservation efforts and human public health alike.

Psychiatry Match Rates Increase After Exposure to a Medical Student Mentorship Program: A Multisite Retrospective Cohort Analysis.

OBJECTIVE: Since 2002, the Klingenstein Third Generation Foundation (KTGF) has supported a network of medical student mentorship programs (MSMPs) across the USA with the explicit aim of enhancing interest in, and eventual recruitment into the field of child and adolescent psychiatry (CAP). The authors conducted a multisite, retrospective cohort analysis to examine the impact of the program on career selection, as reflected by graduation match rates into psychiatry or pediatrics. METHODS: The authors collected graduating match information (2008-2019) from fourteen participating medical schools (Exposed) and thirteen non-participating schools (Control). Control schools were selected based on region, comparable student body and faculty size, national standing, and rank in NIH funding. Match rates into psychiatry and pediatrics were compared between Exposed and Control groups. RESULTS: Exposed schools had significantly higher match rates into psychiatry as compared to unexposed schools (6.1% and 4.8%, respectively; OR [95%CI] = 1.29 [1.18, 1.40]; X2 = 32.036, p < 0.001). In contrast, during the same time period, exposed schools had significantly lower match rates into pediatrics than unexposed ones (11.6 and 10.5%, respectively; OR [95%CI] = 0.89 (0.83, 0.95); X2 = 12.127, p < 0.001). These findings persisted even after adjustment for secular trends in match rates. CONCLUSIONS: Seventeen years after its inception, the KTGF medical student mentorship program network has had a positive impact on match rates into general psychiatry. Future studies will address whether these results translate to trainees' eventual selection of careers in CAP.

The science of the host-virus network.

Better methods to predict and prevent the emergence of zoonotic viruses could support future efforts to reduce the risk of epidemics. We propose a network science framework for understanding and predicting human and animal susceptibility to viral infections. Related approaches have so far helped to identify basic biological rules that govern cross-species transmission and structure the global virome. We highlight ways to make modelling both accurate and actionable, and discuss the barriers that prevent researchers from translating viral ecology into public health policies that could prevent future pandemics.

The three Ts of virulence evolution during zoonotic emergence.

There is increasing interest in the role that evolution may play in current and future pandemics, but there is often also considerable confusion about the actual evolutionary predictions. This may be, in part, due to a historical separation of evolutionary and medical fields, but there is a large, somewhat nuanced body of evidence-supported theory on the evolution of infectious disease. In this review, we synthesize this evolutionary theory in order to provide a framework for clearer understanding of the key principles. Specifically, we discuss the selection acting on zoonotic pathogens' transmission rates and virulence at spillover and during emergence. We explain how the direction and strength of selection during epidemics of emerging zoonotic disease can be understood by a three Ts framework: trade-offs, transmission, and time scales. Virulence and transmission rate may trade-off, but transmission rate is likely to be favoured by selection early in emergence, particularly if maladapted zoonotic pathogens have 'no-cost' transmission rate improving mutations available to them. Additionally, the optimal virulence and transmission rates can shift with the time scale of the epidemic. Predicting pathogen evolution, therefore, depends on understanding both the trade-offs of transmission-improving mutations and the time scales of selection.

The zoonotic potential of bat-borne coronaviruses.

Seven zoonoses - human infections of animal origin - have emerged from the Coronaviridae family in the past century, including three viruses responsible for significant human mortality (SARS-CoV, MERS-CoV, and SARS-CoV-2) in the past twenty years alone. These three viruses, in addition to two older CoV zoonoses (HCoV-229E and HCoV-NL63) are believed to be originally derived from wild bat reservoir species. We review the molecular biology of the bat-derived Alpha- and Betacoronavirus genera, highlighting features that contribute to their potential for cross-species emergence, including the use of well-conserved mammalian host cell machinery for cell entry and a unique capacity for adaptation to novel host environments after host switching. The adaptive capacity of coronaviruses largely results from their large genomes, which reduce the risk of deleterious mutational errors and facilitate range-expanding recombination events by offering heightened redundancy in essential genetic material. Large CoV genomes are made possible by the unique proofreading capacity encoded for their RNA-dependent polymerase. We find that bat-borne SARS-related coronaviruses in the subgenus Sarbecovirus, the source clade for SARS-CoV and SARS-CoV-2, present a particularly poignant pandemic threat, due to the extraordinary viral genetic diversity represented among several sympatric species of their horseshoe bat hosts. To date, Sarbecovirus surveillance has been almost entirely restricted to China. More vigorous field research efforts tracking the circulation of Sarbecoviruses specifically and Betacoronaviruses more generally is needed across a broader global range if we are to avoid future repeats of the COVID-19 pandemic.

A review of mechanistic models of viral dynamics in bat reservoirs for zoonotic disease.

The emergence of SARS-CoV-2, a coronavirus with suspected bat origins, highlights a critical need for heightened understanding of the mechanisms by which bats maintain potentially zoonotic viruses at the population level and transmit these pathogens across species. We review mechanistic models, which test hypotheses of the transmission dynamics that underpin viral maintenance in bat systems. A search of the literature identified only twenty-five mechanistic models of bat-virus systems published to date, derived from twenty-three original studies. Most models focused on rabies and related lyssaviruses (eleven), followed by Ebola-like filoviruses (seven), Hendra and Nipah-like henipaviruses (five), and coronaviruses (two). The vast majority of studies has modelled bat virus transmission dynamics at the population level, though a few nested within-host models of viral pathogenesis in population-level frameworks, and one study focused on purely within-host dynamics. Population-level studies described bat virus systems from every continent but Antarctica, though most were concentrated in North America and Africa; indeed, only one simulation model with no associated data was derived from an Asian bat-virus system. In fact, of the twenty-five models identified, only ten population-level models were fitted to data - emphasizing an overall dearth of empirically derived epidemiological inference in bat virus systems. Within the data fitted subset, the vast majority of models were fitted to serological data only, highlighting extensive uncertainty in our understanding of the transmission status of a wild bat. Here, we discuss similarities and differences in the approach and findings of previously published bat virus models and make recommendations for improvement in future work.

Ecological processes underlying the emergence of novel enzootic cycles: Arboviruses in the neotropics as a case study.

Pathogens originating from wildlife (zoonoses) pose a significant public health burden, comprising the majority of emerging infectious diseases. Efforts to control and prevent zoonotic disease have traditionally focused on animal-to-human transmission, or "spillover." However, in the modern era, increasing international mobility and commerce facilitate the spread of infected humans, nonhuman animals (hereafter animals), and their products worldwide, thereby increasing the risk that zoonoses will be introduced to new geographic areas. Imported zoonoses can potentially "spill back" to infect local wildlife-a danger magnified by urbanization and other anthropogenic pressures that increase contacts between human and wildlife populations. In this way, humans can function as vectors, dispersing zoonoses from their ancestral enzootic systems to establish reservoirs elsewhere in novel animal host populations. Once established, these enzootic cycles are largely unassailable by standard control measures and have the potential to feed human epidemics. Understanding when and why translocated zoonoses establish novel enzootic cycles requires disentangling ecologically complex and stochastic interactions between the zoonosis, the human population, and the natural ecosystem. In this Review, we address this challenge by delineating potential ecological mechanisms affecting each stage of enzootic establishment-wildlife exposure, enzootic infection, and persistence-applying existing ecological concepts from epidemiology, invasion biology, and population ecology. We ground our discussion in the neotropics, where four arthropod-borne viruses (arboviruses) of zoonotic origin-yellow fever, dengue, chikungunya, and Zika viruses-have separately been introduced into the human population. This paper is a step towards developing a framework for predicting and preventing novel enzootic cycles in the face of zoonotic translocations.

Child and Adolescent Psychiatry Perceptions and Career Preference: Participation in a National Medical Student Conference Improves Outcomes.

Since 2002, the Klingenstein Third Generation Foundation (KTGF) has supported a network of medical schools across the country with the explicit aim of enhancing interest in, and eventual recruitment into, the field of child and adolescent psychiatry (CAP). An active component of the KTGF network has been its annual National Medical Student Conference (NMSC).

Host phylogenetic distance drives trends in virus virulence and transmissibility across the animal-human interface.

Historically, efforts to assess 'zoonotic risk' have focused mainly on quantifying the potential for cross-species emergence of viruses from animal hosts. However, viruses clearly differ in relative burden, both in terms of morbidity and mortality (virulence) incurred and the capacity for sustained human-to-human transmission. Extending previously published databases, we delineated host and viral traits predictive of human mortality associated with viral spillover, viral capacity to transmit between humans following spillover and the probability of a given virus being zoonotic. We demonstrate that increasing host phylogenetic distance from humans positively correlates with human mortality but negatively correlates with human transmissibility, suggesting that the virulence induced by viruses emerging from hosts at high phylogenetic distance may limit capacity for human transmission. Our key result is that hosts most closely related to humans harbour zoonoses of lower impact in terms of morbidity and mortality, while the most distantly related hosts-in particular, order Chiroptera (bats)-harbour highly virulent zoonoses with a lower capacity for endemic establishment in human hosts. As a whole, our results emphasize the importance of understanding how zoonoses manifest in the human population and also highlight potential risks associated with multi-host transmission chains in spillover. This article is part of the theme issue 'Dynamic and integrative approaches to understanding pathogen spillover'.

Seasonal trends of nutrient intake in rainforest communities of north-eastern Madagascar.

OBJECTIVE: We collected dietary records over the course of nine months to comprehensively characterize the consumption patterns of Malagasy people living in remote rainforest areas of north-eastern Madagascar. DESIGN: The present study was a prospective longitudinal cohort study to estimate dietary diversity and nutrient intake for a suite of macronutrients, micronutrients and vitamins for 152 randomly selected households in two communities. SETTING: Madagascar, with over 25 million people living in an area the size of France, faces a multitude of nutritional challenges. Micronutrient-poor staples, especially rice, roots and tubers, comprise nearly 80 % of the Malagasy diet by weight. The remaining dietary components (including wild foods and animal-source foods) are critical for nutrition. We focus our study in north-eastern Madagascar, characterized by access to rainforest, rice paddies and local agriculture. PARTICIPANTS: We enrolled men, women and children of both sexes and all ages in a randomized sample of households in two communities. RESULTS: Although the Household Dietary Diversity Score and Food Consumption Score reflect high dietary diversity, the Minimum Dietary Diversity-Women indicator suggests poor micronutrient adequacy. The food intake data confirm a mixed nutritional picture. We found that the median individual consumed less than 50 % of his/her age/sex-specific Estimated Average Requirement (EAR) for vitamins A, B12, D and E, and Ca, and less than 100 % of his/her EAR for energy, riboflavin, folate and Na. CONCLUSIONS: Malnutrition in remote communities of north-eastern Madagascar is pervasive and multidimensional, indicating an urgent need for comprehensive public health and development interventions focused on providing nutritional security.

Climate Change and Global Food Systems: Potential Impacts on Food Security and Undernutrition.

Great progress has been made in addressing global undernutrition over the past several decades, in part because of large increases in food production from agricultural expansion and intensification. Food systems, however, face continued increases in demand and growing environmental pressures. Most prominently, human-caused climate change will influence the quality and quantity of food we produce and our ability to distribute it equitably. Our capacity to ensure food security and nutritional adequacy in the face of rapidly changing biophysical conditions will be a major determinant of the next century's global burden of disease. In this article, we review the main pathways by which climate change may affect our food production systems-agriculture, fisheries, and livestock-as well as the socioeconomic forces that may influence equitable distribution.

Brief Intervention for Heavy Drinking in Primary Care: Role of Patient Initiation.

BACKGROUND: Alcohol brief intervention (BI) in primary care (PC) is effective, but remains underutilized despite multiple efforts to increase provider-initiated BI. An alternative approach to promote BI is to prompt patients to initiate alcohol-related discussions. Little is known about the role of patients in BI delivery. OBJECTIVES: To determine the characteristics of PC patients who reported initiating BI with their providers, and to evaluate the association between the initiator (patient vs provider) and drinking after a BI. METHODS: In the context of clinical trial, patients (n = 267) who received BI during a PC visit reported on the manner in which the BI was initiated, readiness to change, demographics, and recent history of alcohol consumption. Drinking was assessed again at 6-months after the BI. RESULTS: Fifty percent of patients receiving a BI reported initiating the discussion of drinking themselves. Compared with those who reported a provider-initiated discussion, self-initiators were significantly younger (43.7 years vs 47.1 years; P = 0.03), more likely to meet Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria for current major depression (24% vs 14%; P = 0.04), and more likely to report a history of alcohol withdrawal symptoms (68% vs 52%; P < 0.01). Baseline readiness to change, baseline consumption rates, and current DSM-IV alcohol dependence were not different between groups. In the 2 to 3 weeks after BI, self-initiators reported greater decreases in drinks per week (5.7 vs 2.4; P = 0.02), and drinking days per week (1.0 vs 0.3; P = 0.002). At 6-month follow-up, self-initiators showed significantly greater reductions in weekly drinking compared to those whose provider initiated the BI (P = 0.002). CONCLUSIONS: Patient- and provider-initiated BI occurred with equal frequency, and patient-initiated BIs were associated with greater reductions in alcohol use. Future efforts to increase the BI rate in PC should include a focus on prompting patients to initiate alcohol-related discussions.

Brief intervention in alcohol-dependent versus nondependent individuals.

OBJECTIVE: Randomized trials examining the effects of brief alcohol interventions by primary care providers have consistently excluded individuals with alcohol dependence. The purpose of this study was to examine whether a diagnosis of alcohol dependence, according to the criteria in Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, predicted differential effectiveness of a brief intervention (BI). METHOD: Retrospective analyses were performed on participants (N = 326) enrolled in a randomized trial designed to examine the impact of interactive voice response following BI. All participants had received a BI from their primary care provider before enrolling in the study. Daily consumption data were collected using the Timeline Followback for the period before the BI (mean = 71 days) and for 6 months following the BI. We compared nondependent and dependent participants on a number of consumption-based outcomes. RESULTS: Dependent participants had significantly higher pre-BI consumption. At the index assessment (median =15 days after BI), both dependent and nondependent participants reported significant reductions in total drinks per week and drinking days per week after BI. Dependent participants significantly reduced their drinks per drinking day. After BI, dependent participants no longer differed significantly from nondependent participants on these measures. Similar decreases from before BI were observed in both groups through 6 months, although dependent participants drank on fewer days and significantly more on days on which they drank than did nondependent participants. Regression analyses showed that baseline consumption was the only significant predictor of post-BI consumption. CONCLUSIONS: We found no evidence that dependent participants realized less benefit on measures of alcohol consumption following a BI than nondependent participants.

Using interactive voice response to enhance brief alcohol intervention in primary care settings.

OBJECTIVE: Self-monitoring is recommended following brief alcohol intervention (BI). We have previously demonstrated that self-monitoring with an automated telephone system (interactive voice response; IVR) is associated with a steady reduction in alcohol consumption in the absence of BI. In this study we explore the feasibility and efficacy of IVR as a possible therapeutic enhancement for BI. METHOD: We updated all providers (N= 112) in 15 primary care clinics about BI and encouraged them to do a BI with their patients whenever appropriate and to invite those patients to participate in the research project. Interested patients (N = 338) were randomized to one of four study conditions including no IVR and three groups who self-monitored for 6 months using an IVR: no feedback, feedback, and feedback plus a monetary calling incentive. RESULTS: The IVR proved to be a feasible method for self-monitoring. Of those invited to use the IVR, 90% initiated use and made 95% of the calls while they remained engaged with the system; more than half continued calling for the entire 6 months. Reported impact of the IVR and associated feedback on drinking awareness was high. Therapeutic results were mixed. Overall, the IVR groups reported higher consumption on the Timeline Followback (TLFB) at the 3- and 6-month follow-ups than did the no IVR group. However, because of a potential measurement confound, the TLFB may not have operated in an unbiased fashion across the four study conditions. A comparison of the feedback and no feedback IVR groups, which is independent of this confound, shows a significant therapeutic advantage of IVR with feedback. CONCLUSIONS: IVR is a feasible technology for behavioral self-monitoring in primary care clinics. IVR with regular feedback may be an effective therapeutic enhancement to BI.

Should there be both categorical and dimensional criteria for the substance use disorders in DSM-V?

AIMS: As discussed in the following literature review, the relative advantages of categorical and dimensional criteria for classifying the substance use disorders (SUDs) have been debated for many years. The scheduled revision of the Diagnostic and Statistical Manual (DSM) offers an opportunity to re-examine this question. Both categorical and dimensional approaches to diagnosis offer advantages, both may in fact be necessary for a comprehensive taxonomy. METHODS: One means of resolving debate about the direction to take in revising DSM-V and simultaneously of achieving maximum taxonomic utility is to include both categorical and dimensional criteria in DSM-V. This could be accomplished by first defining a set of categorical criteria, as in the previous editions of the DSM. Corresponding dimensional criteria could then be created using a more empirical methodology. In this paper we review some of the relevant literature, offer a specific proposal for a dimensional component for the DSM-V substance use disorders that also preserves the categorical definitions and suggest areas for additional research relevant the this agenda. RESULTS: There is evidence that alcohol and other forms of substance abuse and dependence are heterogeneous categories and that the SUDs can be conceptualized viably as arrayed along a continuum. Amplifying clinically derived categorical definitions with more empirically derived dimensional components to better capture this variability is a particularly important consideration for a substance use research agenda for DSM-V. CONCLUSIONS: It is crucial that a dimensional approach be offered in some form in DSM-V; but it is also vital that any dimensional approach be linked to the categorical definition. The proposal offered herein provides a model for amplifying categorical definitions with a dimensional component in a way that is evolutionary and not disruptive to the existing taxonomy.

Should DSM-V include dimensional diagnostic criteria for alcohol use disorders?

This program calls attention to the upcoming timetable for the revision of the Diagnostic and Statistical Manual (DSM)-IV and the publication of DSM-V. It is vitally important for Research Society of Alcoholism members to be aware of the current discussions of the important scientific questions related to the next DSM revision and to use the opportunity for input. The title of the symposium highlights 1 key question, i.e., whether the DSM definitions should remain strictly categorical as in the past or whether a dimensional component should be included in this revision. Two substantive and 1 conceptual paper are included in this portion of the symposium. The fourth and final presentation detailing the revision timetable and the opportunities for input is by Dr. Darrel Regier. Dr. Regier is the director of American Psychiatric Institute for Research and Education the research and education branch of the American Psychiatric Association and the organization within the APA that will oversee the DSM revision. The discussion is by Marc Schuckit, who was chair of the Substance Use disorders (SUD) Committee for DSM-IV and cochair of the international group of experts reviewing the SUD definitions for DSM-V.