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Y. Anktos, M.A., M.D.

Assistant Professor, Minnesota College of Osteopathic Medicine

Another clinically important issue in this population is addressing poor adherence with both pharmacological and psychosocial interventions. The use of long-acting, injectable antipsychotic medications can help increase medication adherence. A long-acting, injectable form of the second-generation antipsychotic risperidone is available as are long-acting decanoate preparations of first-generation antipsychotics. In general, medications targeting specific substance use disorders can be safely prescribed for patients with co-occurring schizophrenia and substance use disorders (288). However, careful assessment is indicated before initiating treatment with disulfiram. Given the cognitive difficulties associated with schizophrenia, disulfiram should be reserved for use in individuals whose judgment and memory are adequate and for whom impulsivity is not a significant concern. In addition, there may be some further concern about using high-dose disulfiram in this population because carbon disulfide, a metabolite of disulfiram, inhibits dopamine -hydroxylase, increases dopamine levels, and could potentially worsen psychosis (409, 410). Specific studies also support the use of naltrexone for alcohol dependence and methadone for opioid dependence in this population (411­413). There is a theoretical concern that bupropion may increase psychotic symptoms; however, this concern has not been borne out in studies to date (414). One key aspect of integrated treatment is that patients do better when clinicians are able to maintain an optimistic, empathic, and helpful approach (417). Integrated programs often provide comprehensive services, including active outreach and case management in the community setting, in an effort to better engage and retain patients and help them transition between different levels of care (370, 417). Other helpful components to integrated treatment programs include contingency management and money management (360, 372). Money management helps patients prevent relapse, given that many receive Social Security disability or Supplemental Security Income payments and are most vulnerable to substance use and relapse soon after receiving these funds (372). Depressive disorders Major depressive and substance use disorders commonly co-occur in clinical populations and in the community (341, 343, 344, 420). Studies have demonstrated that individuals diagnosed with major depressive disorder have high lifetime co-occurrence rates of alcohol abuse (men 9% and women 30%) and alcohol dependence (men 24% and women 48. Among individuals with major depressive disorder, approximately 25% have a co-occurring substance use disorder (422). A large prospective, longitudinal study has demonstrated that alcohol and drug use disorders during adolescence predict later development of major depressive disorder in young adults (423). Mood disturbance is one of the most common symptoms reported by individuals in substance use disorder treatment programs. In addition to the high rate of co-occurring major depressive and substance use disorders, patients in substance use disorder treatment settings frequently experience substance-induced mood disorders in which signs and symptoms of depression are related to acute substance intoxication or to acute or protracted withdrawal from substances; these symptoms remit with maintained abstinence (424). Because it is often difficult for a clinician to discern whether a cluster of symptoms is due to co-occurring major depressive disorder, substance intoxication, substance withdrawal, substance-induced mood Treatment of Patients With Substance Use Disorders 53 Copyright 2010, American Psychiatric Association. When possible, it is advisable to delay antidepressant pharmacotherapy by 1­4 weeks, depending on the nature and severity of the mood symptoms, to allow the clinician to identify substance-induced mood symptoms that may remit without medication intervention. In general, treatment of depressive symptoms of moderate to severe intensity should begin concurrently or soon after initiating treatment of the co-occurring substance use disorder, particularly if there is evidence of prior mood episodes. In individuals without prior episodes of depression or a family history of mood disorders, it may be appropriate to delay the treatment of mild to moderate depressive symptoms for the purpose of diagnostic clarification. Clinicians are advised to monitor symptoms, assess and reassess for suicidal ideation, provide education, encourage abstinence from substances, and observe changes in mental status during the substance-free period while actively considering whether antidepressant intervention is indicated (288, 426­429). Randomized, controlled trials supporting the efficacy of antidepressant pharmacotherapies for co-occurring major depressive disorder and specific substance use disorders exist for alcohol dependence, opioid dependence, cocaine use disorders, and nicotine dependence. A meta-analysis of 14 well-designed placebo-controlled trials of antidepressant medication for co-occurring major depression and alcohol, opioid, or cocaine dependence (425) showed an overall beneficial effect of medication on mood outcome, similar in magnitude to the effect size observed in clinical trials involving depressed patients without substance problems. Studies showing the largest effects of medication on mood outcome also showed significant beneficial effects of medication on self-report measures of substance use, although rates of abstinence were low. The results across studies were inconsistent, with eight positive and six negative studies. The positive studies, those demonstrating a beneficial effect of antidepressant medication, had low placebo response rates and were more likely to have required at least a week of abstinence prior to diagnosing depression and starting medication.

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Yet there are significant lags in moving from discovery to extraction of resources, sometimes over one or even two decades. With this in mind, it is not unreasonable for most countries and their donors and production partners to embark down the path of extraction, with the hope that the conditions for welfare-enhancing use of rents will improve over time. In some cases, to be sure, elite capture of natural resource rents subverts the achievement of sustainable development outcomes. But even well-intentioned leaders often confront daunting challenges in implementing welfare-enhancing policies. While a leader today may be interested in saving resources for the future, for example, she may simply not trust her successors to later spend them well, given weak institutional checks and balances. Or, new reform-minded governments may find that vested interests and corrupt practices in the resource sector are too pervasive to be easily overcome with policy directives. This book emphasizes actions that committed domestic agents, international development partners, and responsible stakeholders in the global extractive industries can take to enhance the prospects of a resource-dependent developing country by grounding interventions in a granular understanding of the common political economy dynamics surrounding natural resources. Dependence on natural resources Introduction: Beyond the Resource Curse 9 shapes state institutions and the decision-making framework and calculus facing political and economic elites, which affects the possibility of achieving the higher-order objectives that can aid in overcoming adverse outcomes, such as the need to deepen institutionalization, to bolster credibility, and to extend time horizons. Tailored operational recommendations are needed to achieve such goals, for example, measures to increase transparency in contract negotiations, enhance tax administration capacity, or improve the prioritization of public investment. And the targets of these specific forms of intervention are natural resource sector policies, institutions, and governance. A policy may be enacted in legislation or underpinning regulation; natural resource policies are often made explicit in a minerals law, for example. Institutions are the "rules of the game" that structure political, economic, and social interactions. With respect to natural resources, formal institutions could include legislation on the natural resource sectors or a fiscal equalization formula for transfers from resource-rich provinces to those that are resource-poor. Informal institutions encompass the unwritten rules structuring behavior; for example, there may be implicit social obligations being acted upon. Governance is the exercise of public authority with regard to society through the agencies of government-executive, legislature, judiciary- in the context of the institutional and policy framework in place. It is about the processes by which bargains between state and society are made (including policies and institutions) and how they are subsequently implemented and monitored (by organizations). State capacity, or the ability of the state to implement policy through its agencies, is an important aspect of governance. Weak institutions and low-capacity public sector agencies in resourcedependent developing countries mean that the ability of the state to make policy decisions to mitigate the resource curse will be equally weak. Understanding how natural resource extraction interacts with institutions and governance to cumulate into broader political economy trajectories is crucial for elaborating potential developmental assistance. Furthermore, development partners may, in collaboration with reformist clients, adopt an even more transformative stance regarding institutions; again, success will hinge on a firm grasp of the political economy of natural resource dependence. Transforming Rents into Riches Natural resources yield "rents," or extraordinary profits from their production, which are crucial to the political economy of resource-led development. Chapter 2 reviews the scholarship on the "rentier state" and how resource rents interact with institutions and political economy dynamics, then develops a core political economy framework for this volume that rests on understanding how rents flow through the system. Provided here is a brief overview of the analytical logic that animates this work. Many different domestic and international stakeholders are involved in natural resource policy making and extraction, and the relationships among these actors are constantly shifting across the value chain. Political economy scholarship often relies on regime typologies to distinguish why certain types of country settings yield certain outcomes. In order to help country counterparts and development practitioners diagnose the political economy trajectory a resource-dependent country is embarked upon, this volume advances a simple typology that is structured around two crucial dimensions: · · the credibility of intertemporal commitment-or the degree to which policy stability and bargains over time can be enforced and deviations from such agreements are subject to sanction; and the overall political inclusiveness of the prevailing state-society compact-or the extent to which diverse social, economic, and political viewpoints are incorporated into decision-making, and a sense of either collectivist or clientelist welfare is privileged over purely elite interests. Although these dimensions are interdependent to some extent, positioning them against each other yields a typology of four distinct country settings (table 1. Characterizations of each setting, as well as unbundled components underlying each dimension, can be found in chapter 2.

Annotated genomes allow us to compare genes descended from the same ancestor across many different organisms. Sometimes this comparative genomic approach allows us to assign putative functions to unknown predicted genes. The simultaneous publication of three Aspergillus genome manuscripts in Nature in December 2005 established Aspergillus as the leading filamentous fungal genus for comparative genomic studies (Nierman et al. Like most major genome projects, these Aspergillus efforts were collaborations between a large sequencing centre and the respective community of scientists. Aspergillus species are only one group among a large number of eukaryotes now catalogued in databanks. There are currently well over 100 fungal genome projects in various stages of com- An Overview of the Genus Aspergillus 13 pletion (see. Our expectations for genome projects have become higher than they were just a few years ago. Now we hope to become genomic detectives using sequence similarities to find new enzymes, secondary metabolites and other biologically important gene products. Since visible phenotype is a manifestation of many genes and pathways acting together, the high genomic identity merely confirms what taxonomists have known since they first described the A. When Thom and Church published the first major monograph on the genus Aspergillus in 1926 they pointed out that although the type cultures of A. The morphological, physiological and genomic correspondence between the species is all the more remarkable because of their differing 14 Bennett caister. In: the Aspergilli: Genomics, Medical Aspects, Biotechnology, and Research Methods, Goldman, G. Fungal Disease of Animals (Bucks: Farnham Royal Commonwealth Agricultural Bureau). A ferment of fermentations: reflections on the production of commodity chemicals using microorganisms. Comparative genomics data can be leveraged to characterize biosynthetic processes. Together with advanced bioinformatics and data analysis tools, we are gaining new insights into the functional properties and activities of Aspergillus fungal genomes. Our ability to acquire genome-wide data has not enlightened us about the mechanics of pathogenicity and competitiveness, and at the broadest ecological level we are still a long way from understanding why some species are common whereas others are rare. Experimental characterization and functional analysis remain the rate limiting steps in translating genomics data into the drug discovery pipeline as well as for harnessing other aspects of Aspergillus metabolism. New ways to connect traditional biology, gene function and evolution are on the horizon. Aspergillus species remain resilient models for studying basic questions in eukaryotic biology. Undoubtedly, Aspergillus genomics will enlighten fundamental insights into cell biology as well as have important implications for agriculture, industry and medicine. The forthcoming chapters in this volume review the current state of knowl- caister. In: the Genus Aspergillus: From Taxonomy and Genetics to Industrial Application, Powell, K. Fungal Pathogenesis: Principles and Clinical Applications (New York: Marcel Dekker. Daily asthma severity in relation to personal ozone exposure and outdoor fungal spores. An Overview of the Genus Aspergillus 15 In: Advances in Penicillium and Aspergillus systematics, Samson, R. A review of molecular phylogenetics in Aspergillus, and prospects for a robust genus-wide phylogeny. Aflatoxin: Scientific Background, Control, and Implications (New York: Academic Press). Possibilities to amend or delete Article 59 of the International Code of Botanical Nomenclature to achieve a unified nomenclature and classification of the fungi.

The work of psychotherapy itself may generate anxiety or other strong feelings, which may be difficult for patients to manage. An indirect measure of the relative side effects and tolerability of psychotherapy can be obtained from the dropout rates in clinical trials; however, many other factors can also affect these rates. Depending on what can reasonably be expected with the given type of psychotherapy, the psychiatrist should consider a change in the intensity or 47 type of psychotherapy and/or addition or change to medication if psychotherapy for major depressive disorder has not resulted in significant improvement in 4­8 weeks. Cognitive and behavioral therapies In the treatment of depressed patients, psychotherapies that focus primarily on aspects of cognitive patterns and those that emphasize behavioral techniques can be used alone, but are generally used in combination. Cognitivebehavioral therapy combines cognitive psychotherapy with behavioral therapy and maintains that irrational beliefs and distorted attitudes toward the self, the environment, and the future perpetuate depressive affects and compromise functioning. Cognitive-behavioral therapy is an effective treatment for major depressive disorder. Behavior therapy for major depressive disorder is based on theoretical models drawn from behavior theory (301) and social learning theory (302). Behavioral activation is a newly articulated behavioral intervention with some positive preliminary results that merit further study (288, 303). Specific behavior therapy techniques include activity scheduling (304, 305), self-control therapy (306), social skills training (307), and problem solving (308). Behavior therapy involves graded homework, scheduling of enjoyable activities, and minimizing unpleasant activities (309). Behavior therapy has demonstrated efficacy, at times superior to cognitive therapy, in treating major depressive disorder (310). Interpersonal psychotherapy is an efficacious treatment for major depressive disorder (296, 313). Studies have shown efficacy of this treatment in depressed primary care patients and patients with more severe depression (311). Interpersonal psychotherapy can also be used as a monthly maintenance therapy to prevent relapse (289, 314, 315). Psychodynamic psychotherapy the term "psychodynamic psychotherapy" encompasses a range of brief to long-term psychotherapeutic interventions (318­320). These interventions derive from psychodynamic theories about the etiology of psychological vulnerability, personality development, and symptom formation as shaped by development and conflict occurring during the life cycle from earliest childhood forward (321­ 325). Some of these theories focus on conflicts related to guilt, shame, interpersonal relationships, the management of anxiety, and repressed or unacceptable impulses. Others address developmental psychological deficits produced by inadequacies or problems in the relationship between the child and emotional caretakers, resulting in problems of self-esteem, sense of psychological cohesiveness, and emotional self-regulation (323, 326­330). Psychodynamic psychotherapy may be brief but usually has a longer duration than other psychotherapies, and its aims extend beyond immediate symptom relief. Psychodynamic psychotherapy is therefore broader than most other psychotherapies, encompassing both current and past problems in interpersonal relationships, self-esteem, and developmental conflicts associated with anxiety, guilt, or shame. Sometimes a goal of psychodynamic psychotherapy, brief or extended, may be to help the patient accept or adhere to necessary pharmacotherapy (331). Although psychodynamic psychotherapy is often used in clinical practice, its efficacy in the acute phase of major depressive disorder remains less well studied in controlled trials than the efficacy in this phase of some other forms of psychotherapy. Problem-solving therapy Problem-solving therapy is a manual-guided, brief treatment lasting six to 12 sessions. This therapy, often administered by nurses or social workers, has been used to prevent depression in elderly and/or medically ill patients, and it has also been used to treat patients with relatively mild depressive symptoms. Some studies have reported modest improvement in patients with mild depressive symptoms. Although problem solving therapy has had limited testing for patients with major depressive disorder, it may have a role in targeted patient populations with mild depression (332­335). Marital therapy and family therapy Marital and family problems are common in the course of mood disorders, and comprehensive treatment often demands assessing and addressing these problems. Marital and family problems may be the consequence of major depressive disorder but may also increase vulnerability to developing major depressive disorder or retard recovery from it (336­339).