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Nitrilases are important in the biosphere as participants in synthesis and degradation pathways for naturally occurring, as well as xenobiotically derived, nitriles. Because of their inherent enantioselectivity, nitrilases are also attractive as mild, selective catalysts for setting chiral centers in fine chemical synthesis. Unfortunately, <20 nitrilases have been reported in the scientific and patent literature, and because of stability or specificity shortcomings, their utility has been largely unrealized. In this study, 137 unique nitrilases, discovered from screening of >600 biotope-specific environmental DNA (eDNA) libraries, were characterized. Using culture-independent means, phylogenetically diverse genomes were captured from entire biotopes, and their genes were expressed heterologously in a common cloning host. Nitrilase genes were targeted in a selection-based expression assay of clonal populations numbering 10(6) to 10(10) members per eDNA library. A phylogenetic analysis of the novel sequences discovered revealed the presence of at least five major sequence clades within the nitrilase subfamily. Using three nitrile substrates targeted for their potential in chiral pharmaceutical synthesis, the enzymes were characterized for substrate specificity and stereospecificity. A number of important correlations were found between sequence clades and the selective properties of these nitrilases. These enzymes, discovered using a high-throughput, culture-independent method, provide a catalytic toolbox for enantiospecific synthesis of a variety of carboxylic acid derivatives, as well as an intriguing library for evolutionary and structural analyses.

The evolution of NOx from grass and maize silages was measured using chemiluminescence in samples kept in airtight containers, in the silos and in a 750 kg mass removed to a mixer waggon. Measurements were made on the grass and maize silos in two consecutive years. The results show that there is continuous evolution of NOx after silos have been opened and that high concentrations persist in the mass which are rapidly released on agitation at the feed-out. The maximum recorded concentrations of NO and NO2 were 1985 and 152 ppbv respectively. These values are orders of magnitude greater than for rural background levels and exceed the maximum hourly exposure of 50 ppbv for NO2 recommended by the UK expert panel for quality standards.

Background: Trauma is a necessary diagnostic criterion for post-traumatic stress disorder (PTSD). However, the nature of traumas experienced (e.g. assaultive versus non-assaultive) may influence whether any mental disorder will arise. Traumatic experiences may also be associated with other mental disorders, particularly major depressive disorder (MDD). This report examines the relationship of trauma history to the likelihood of full or partial PTSD and MDD. In addition, the study examines the frequency with which assaultive and non-assaultive traumas are reported by patients with full or partial PTSD and MDD., Methods: Three hundred eighty-six primary care patients completed psychiatric symptom measures during their clinic visit. A subset of 132 participants completed a diagnostic interview within 2 weeks following the screening., Results: Most patients reporting traumas did not meet criteria for a mental disorder. Patients reporting traumas were more likely to experience current MDD (27.8%) than current full or partial PTSD (20.0%) although a high percentage of patients with traumas (41.1%) had experienced full or partial PTSD diagnosis in their lifetime. Respondents reporting assaultive events as their most severe trauma, when compared with those whose most severe trauma was non-assaultive, were more likely to have met criteria for either full or partial PTSD in their lifetime, and were more likely to have current MDD., Conclusions: These findings suggest that trauma history is often not associated with psychopathology, and when it is, trauma is often associated with major depression rather than PTSD. The likelihood of psychopathology is increased for individuals reporting assaultive traumas.

There is considerable evidence that psychosocial treatments benefit younger adults with schizophrenia. However, no studies have been undertaken of such interventions for older patients with schizophrenia. This report describes the development of a novel integrated treatment combining cognitive-behavioral therapy (CBT) and social skills training (SST). This intervention is designed to address the needs of older patients with schizophrenia by challenging beliefs common in this population that interfere with treatment and by providing repetitive practice of behaviors to improve retention and skill development. The authors provide two case reports and pilot data suggesting benefits of this approach.

Recent exploratory [Taylor, S., Kuch, K., Koch, W. J., Crockett, D. J., & Passey, G. (1998). The structure of posttraumatic stress symptoms. Journal of Abnormal Psychology, 107, 154-160.] and confirmatory [Buckley, T. C., Blanchard, E. B., & Hickling, E. J. (1998). A confirmatory factor analysis of posttraumatic stress symptoms. Behaviour Research and Therapy, 36, 1091-1099; King, D. W., Leskin, G. A., King, L. A., & Weathers, F. W. (1998). Confirmatory factor analysis of the clinician-administered PTSD scale: evidence for the dimensionality of posttraumatic stress disorder. Psychological Assessment, 10, 90-96.] factor analytic investigations suggest that the three symptom clusters of posttraumatic stress disorder (PTSD) as defined in the Diagnostic and Statistical Manual [4th ed.; DSM-IV; American Psychiatric Association (1994). Diagnostic and statistical manual of mental disorders (4th ed.). Washington, DC: Author.] may not provide the best conceptualization of symptom dimensionality. However, the alternative models have not been in agreement, nor have they been compared against each other or models based on the DSM-IV. The purpose of the present investigation was to test a series of dimensional models suggested by these recent factor analytic investigations and the DSM-IV. Using data collected with the PTSD Checklist--Civilian Version [Weathers, F. W., Litz, B. T., Huska, J. A., & Keane, T. M. (1994). PCL-C for DSM-IV. Boston: National Center for PTSD--Behavioral Science Division.] from 349 referrals to a primary care medical clinic, we used confirmatory factor analysis to evaluate a: (1) hierarchical four-factor model, (2) four-factor intercorrelated model, (3) hierarchical three-factor model, (4) three-factor intercorrelated model, and (5) hierarchical two-factor model. The hierarchical four-factor model (comprising four first-order factors corresponding to reexperiencing, avoidance, numbing, and hyperarousal all subsumed by a higher-order general factor) provided the best overall fit to the data; although, all models met some standards specified for good model fit. More research is needed to establish the dimensional nature of PTSD symptoms and to assess whether identified dimensions differ as a function of the trauma experience. Implications for assessment, diagnosis, and treatment are also discussed.

Patients seen in primary medical clinics report higher rates of major depression [Pérez-Stable et al., 1990: Arch Intern Med 15:1083-1088], and panic disorder [Sherbourne et al., 1996b: Von Korff et al., 1987: Arch Gen Psychiatry 44:152-156] than the general population. Primary care staff therefore need efficient methods of identifying patients with psychiatric disorders. The current study evaluates the use of several brief psychiatric screening measures for identifying patients with major depression and/or anxiety disorders. Participants were 213 primary care patients who received the Center for Epidemiological Studies Depression Scale (CES-D), the Beck Anxiety Inventory (BAI), and two new instruments, the Autonomic Nervous System Questionnaire (ANS) for assessing panic disorder and the Social Phobia Questionnaire (SPQ) for assessing social phobia. Participants received both the screening instruments and a structured diagnostic interview. Results suggest that the CES-D is a useful measure for detecting psychopathology, but it is not particularly specific to depression, the ANS was a highly sensitive and reasonably specific measure for panic disorder, and the SPQ was reasonably sensitive and specific for social phobia. The BAI was a relatively poor screening measure that added no significant information beyond the other measures.

Men in alcohol dependence treatment commonly report elevated levels of stressful life experiences prior to entering treatment. Clinical researchers have argued that training patients to cope with stress is an important aspect of therapy for alcohol dependence. Current age and age of onset of alcohol dependence are two patient characteristics that may relate to stress and allow mental health care providers to anticipate patient needs more readily. This study examines whether current age and age of onset of alcohol dependence are related to the type of stress experienced preceding treatment. Participants were 350 male veterans receiving inpatient treatment for alcohol dependence who completed a semistructured interview-based life stress assessment. The likelihood of life events related to achievement, relationship, and legal problems decreased with age; the likelihood of health difficulties increased with age; and age and age of onset of alcohol dependence interacted to predict health difficulties. These results indicate that the nature of some stress experiences prior to treatment for alcohol dependence may be related to current age and the course of alcohol dependence.

Background: This study assesses depression among primary care patients, the relationship between depression and functioning, and how frequently depressed individuals receive mental health treatment., Methods: Two hundred and thirteen participants completed a diagnostic interview and measures of functional impairment and service utilization., Results: Sixty-two clinic patients were depressed, and depressed individuals experienced significant functional impairment even after controlling for comorbid anxiety disorders and medical problems. However, less than 40% of depressed individuals were receiving treatment for depression. Severity of impairment was related to likelihood of receiving mental health services., Limitations: Several factors to consider when evaluating this study are the cross-sectional design, use of self-report data, and lack of random sampling., Conclusions: These results show that depression has a unique and significant impact on the functioning of primary care patients, and emphasize the need for identification of depressive disorders in primary care.

Clinical depression is frequently unrecognized, even in health care settings. This study (a) reports high levels of major depressive episodes (MDEs) and depressive symptoms in a public sector women's clinic, (b) compares computerized voice recognition with live interviews, and (c) compares Spanish and English versions of the depression-screening instruments. Patients (N = 104) completed face-to-face interviews and/or computerized voice recognition interviews in counterbalanced order; 38% scored positive for current MDE, and 67% scored positive for lifetime MDE. The mean score on the Center for Epidemiological Studies Depression scale (CES-D) was 22.1 (SD = 12.1), with 68% scoring 16 or above. No differences were found on either measure between English and Spanish speakers. Overall agreement between computer and live interviews was as follows: kappa = .82 for both current and lifetime MDE and r = .89 for CES-D scores. Kappas between the MDE Screener developed for this study and the Primary Care Evaluation of Mental Disorders were .75 for live interviews and .81 for the computerized version. Depression screening with computerized voice recognition methods yielded results comparable with those of live interviews in both English and Spanish.

Background: Social phobia (social anxiety disorder) is a common disorder that is receiving more attention as new treatments become available. Little is known about social phobia as it appears in the primary care setting. The purpose of our study was to determine the prevalence of social phobia in a primary care clinic, the rates of comorbidity with other anxiety and mood disorders, the extent of disability, and patterns of healthcare utilization., Methods: A total of 511 English-speaking adults presenting for routine medical care participated in a 2-stage screening consisting of the administration of a self-report measure for social phobia followed by a structured diagnostic interview. We determined current (1-month) prevalence of social phobia, current comorbid disorders, and we ascertained use of health care in the previous 6 months. We also administered brief functional impairment and disability indices., Results: A lower-bound estimate of 7.0% of primary care attendees suffered from social phobia as defined in the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition. Comorbidity with major depression (58.3% of cases of social phobia) was extensive, somewhat less so with panic disorder (27.8%) and generalized anxiety disorder (30.6%). Social phobics reported significantly more impairment in all functional domains than primary care patients without mental disorders; this was most pronounced in patients with the generalized subtype of social phobia. Social phobics made greater use of health care resources than patients who were not mentally ill, yet few (<20%) were receiving appropriate psychotropic medications., Conclusions: Patients with social phobia frequently present to primary care medical settings, and manifest impairment in multiple functional domains. But, on the basis of the low rate of psychotropic prescription, it seems that social phobia is either undiagnosed or felt by physicians to be unlikely to benefit from such treatments. Social phobia is highly comorbid with major depression and with other anxiety disorders in the primary care setting. Attention by family physicians to the presence of depression or panic attacks should signal the need to query patients about possible social phobia.

Background: Increased medical service utilization in patients with panic disorder has been described in epidemiologic studies, although service use in primary care panic patients relative to other primary care patients is less well characterized. Inadequate recognition of panic has been shown in several primary care studies, although the nature of usual care for panic in this setting has not been well documented. This study aimed to document increased service use in panic patients relative to other primary care patients and to characterize the nature of their usual care for panic and their outcome., Method: Using a waiting room screening questionnaire and follow-up telephone interview with the Composite International Diagnostic Interview, we identified a convenience sample of 81 patients with panic disorder (DSM-IV) and a control group of 183 psychiatrically healthy patients in 3 primary care settings on the West Coast and determined psychiatric diagnostic comorbidity, panic characteristics, disability, and medical and mental health service use, including medications. A subsample (N = 41) of panic patients was reinterviewed 4-10 months later to determine the persistence of panic and the adequacy of intervening treatment received using the Harvard/Brown Anxiety Disorders Research Program study criteria for cognitive-behavioral therapy (CBT) and an algorithm developed by the authors for medications., Results: Seventy percent of panic patients had a comorbid psychiatric diagnosis. Patients had more disability in the last month (days missed or cut down activities) (p < .01), more utilization of emergency room and medical provider visits (p < .01), and more mental health visits (p < .05). Despite the latter, only 42% received psychotropic medication, 36% psychotherapy, and 64% any treatment. On follow-up, 85% still met diagnostic criteria for panic, and only 22% had received adequate medication (type and/or dose) and 12% adequate (i.e., CBT) psychotherapy., Conclusion: These findings suggest a need for improved treatment interventions for panic disorder in the primary care setting to decrease disability and potentially inappropriate medical service utilization.

We examined the relation between stressful life events and drinking outcome among 129 male alcoholics who had completed an alcohol treatment program. Life events were assessed for the year prior to treatment and for the 3 months after treatment and were rated on the Psychiatric Epidemiology Research Interview and the Contextual Rating System. Approximately 40% of the pretreatment stressors were found to be directly or indirectly related to alcohol use. When stressors related to drinking were excluded from consideration, we found that men who returned to drinking after treatment experienced more severe or highly threatening stress before their relapse than men who remained abstinent during the follow-up period. These data suggest that although less severe stress may not increase risk for relapse, acute severe stressors and highly threatening chronic difficulties may be associated with elevated relapse risk.

After the diagnosis of MEN IIa syndrome in five members of a British family, a further 180 members were identified, 167 of whom were still alive. From death certificates, a further three were found to have been affected. Of these eight patients, only two were diagnosed and survived. Over the next four years, these two survivors and 90 others (those over the age of ten years) attended a screening program using alcohol or pentagastrin stimulated plasma calcitonin for MCT or urinary catecholamines for pheochromocytoma. The two surviving patients and 12 others were thought to have abnormal screening tests. One patient with an abnormal catecholamine excretion level had bilateral pheochromocytomas removed. Of the 13 patients with abnormal stimulated plasma calcitonin levels, five underwent total thyroidectomy, but MCT was found in only two. One of these patients and two of those in whom no tumor was found had persistently elevated stimulated plasma calcitonin levels postoperatively, suggesting the presence of C cells and, thus, persisting risk of MCT. In all patients, plasma calcitonin concentrations were variable, and an established normal range of values is essential if unnecessary surgical treatment is to be avoided. Pheochromocytoma proved difficult to diagnose, and pentagastrin stimulated plasma catecholamines deserves evaluation as a screening test. Despite the large effort involved, permanent screening of all family members is recommended as the only means of reducing mortality. Following any treatment, screening should continue because new disease or recurrence is possible.