British Journal of Psychiatry (1995), 167, 343-349Since the classic study of Ingvar & Franzen (1974),there have been many investigations of schizophreniaby functional brain imaging (Andreasen eta!, 1992).Most (—‘6001o)have observed a relative reduction infrontal metabolism in patients scanned at rest(hypofrontality). However, many studies (—400lo)found no evidence of hypofrontality and a fewobserved hyperfrontality. There are good reasons whyresting scans of schizophrenic patients should lead tocontradictory results. Mental activity is associatedwith detectable brain activity even when no overtbehaviour occurs (e.g. Stephan et al, 1995).Schizophrenic patients vary widely in their currentmental state, and thus varying patterns of cerebralblood flow are to be expected in unselected groups.Liddle eta! (1992) confirmed that current symptomsare related to regional cerebral blood flow (rCBF).Hypofrontality (particularly in the left dorsolateralprefrontal cortex (DLPFC)) wasfound to be associatedwith psychomotor poverty (poverty of speech,flattening of affect, and motor retardation).However, even though schizophrenic symptomssegregate into clusters, and different patterns ofresting cerebral blood flow can be associated withthese syndromes, it remains likely that a coreabnormality is present in all schizophrenic patients.An important approach to the problem of thevariability in mental states during brain imaging isto control mental state, at the time of scanning, byapplying a psychological challenge. This involvespresenting a task during the scan which elicitsspecificmental processes. This method can not only reducevariability between subjects, but also highlight brainareas of interest. For this purpose, various studieshave used psychological tasks sensitiveto frontal lobedamage. When normal volunteers perform suchtasks, there is an associated increase in frontal bloodflow. However, in schizophrenic patients, whoperform such tasks poorly, this increase is oftenreduced or absent (Weinberger, 1986). Thisobservation is particularly marked in patients withnegative features (Andreasen et a!, 1992). At the

ISSUE: Over 11,000,000 diagnostic endoscopies are performed annually in the United States. Endoscopes are also used in surgery, intubation, and for other therapeutic purposes. Reprocessing endoscopes involves manual cleaning followed by high level disinfection, which is often performed in automated endoscopic reprocessors. There are multiple steps in which deficiencies can occur, including personnel failure to perform a necessary step and equipment malfunction. The California Department of Health Services (CDHS) has encouraged facilities that perform endoscopies to report deficiencies and consults with them on their response.

ISSUE: Norovirus outbreaks are common, occur seasonally, and disproportionately affect long-term care facilities (LTCF), particularly skilled nursing facilities (SNF), where the transmission is almost always person-to-person. In 2002 the California Department of Health Services recognized that the etiology and nature of transmission of such outbreaks were often not recognized, and therefore poorly reported, investigated or controlled. PROJECT: A series of interventions were implemented to improve the control of norovirus outbreaks in California LTCF. A guideline for the control of outbreaks of acute gastroenteritis was developed and distributed to all licensed healthcare facilities, local health departments (LHD), and licensing and certification (L&C) offices in December 2002 and annually thereafter. Sample line listings for ill residents and staff and a sample summary log were included, and facilities encouraged or, in some cases, required by LHD or L&C to be reported. A guideline for the investigation of norovirus outbreaks was developed and distributed to LHD and L&C offices in December 2003. Because of ongoing questions from LHD, a control checklist and supplemental guidelines in the form of questions and answers were distributed in December 2006 and January 2007. Where line listings were available, epidemiologic curves were generated and examined for efficacy of control interventions. RESULTS: The initial publication of the guideline was followed by an immediate increase in reports of outbreaks to local health departments and L&C offices. In 2007, in response to an apparent increase in outbreaks compared to previous years, issues not anticipated in the guidelines arose from LHD and were addressed in supplemental guidelines. Issues included closure of the facility to new admissions and/or visitors, restriction of workers from working at other facilities, the duration of exclusion of ill employees, restriction of asymptomatic residents to their rooms (quarantine), use of alcohol hand hygiene products, and methods of cleaning and disinfection including the use of disinfectants registered by the Environmental Protection Agency (EPA) as effective against norovirus. Some epidemiologic curves showed rapid diminutions in daily case counts, possibly in association with implementation of recommended control measures, while others continued for weeks until resident attack rates of reached 50-70%. Control appeared to be unlikely when four or more of residents became ill on a single day, often anecdotally associated with residents or staff vomiting in a location that exposed multiple persons and/or contaminated frequently touched and difficult to clean environmental surfaces. LESSONS LEARNED: Outbreaks of norovirus are common in LTCF, occur seasonally, and are transmitted person-to-person propagated by direct exposure to vomitus and contact with ill persons and contaminated environmental surfaces. The key to containment is early recognition and implementation of control measures. Specific studies to determine best methods to achieve control are needed.

It has been suggested that certain characteristic symptoms of schizophrenia reflect a specific deficit in the ability to attribute mental states to others (‘mentalizing’). Patients with negative features, particularly social withdrawal and blunted affect, those with thought disorder and patients with paranoid symptoms have difficulties when they try to infer what is going on in the minds of other people. This study examines this notion using two sets of cartoon jokes. While the first set can be understood purely using physical and semantic analysis, the second set requires that the viewer appreciates the mental state of the main character in order to ‘get’ the joke. For control subjects there was no difference in the ability to understand the two types of joke, while the schizophrenic patients found the mental state jokes significantly more difficult to understand. This effect was most marked in patients with behavioural disorders and those reporting passivity experiences. Those with paranoid delusions also showed a selective comprehension deficit with the mental state stimuli. Patients who were symptom free at the time of testing showed normal performance.

Measurements of the electron coefficients of Al2O3 surfaces bombarded by protons, deuterons, alphas and single ionized hydrogen molecules are presented. The 76 "-cyclotron of the Crocker Nuclear Laboratory of the University of California was used to accelerate those ions in the range of 10 to 80 MeV. The data has been compared to theoretical predictions and to previous experimental work. For Z=1 the yields are consistent with the scaling of the stopping power with the ion mass. For Z=2 the results agree well for energies above 40 MeV. At lower energies the yields are lower than predicted.

Background. This study examined the pattern of cerebral blood flow observed in chronic schizophrenic patients while they performed a paced verbal fluency task. Such tasks engage a distributed brain system associated with willed action. Since willed action is impaired in many chronic schizophrenic patients we hypothesised that task performance would be associated with an abnormal pattern of blood flow.Method. Positron emission tomography (PET) was applied to 18 chronic schizophrenic patients stratified into three groups on the basis of verbal fluency performance and current symptoms. Regional cerebral blood flow (rCBF) was measured while the patients performed (a) verbal fluency, (b) word categorisation, and (c) word repetition. Results were compared with six normal controls matched for age, sex and premorbid IQ. Analysis was restricted to six brain regions previously identified in studies of normal volunteers.Results. In five brain areas, including the left dorsolateral prefrontal cortex, the patients showed the same pattern of activation as control subjects. However, in the left superior temporal cortex, all patient groups failed to show the normal decrease in blood flow when verbal fluency was compared with word repetition.Conclusion. These observations suggest that (a) chronic schizophrenic patients can show a normal magnitude of frontal activation when matched for performance with controls, and (b) they fail to show the expected reductions of activity in the superior temporal cortex. This latter result may reflect abnormal functional connectivity between frontal and temporal cortex.

HALLUCINATIONS, perceptions in the absence of external stimuli, are prominent among the core symptoms of schizophrenia. The neural correlates of these brief, involuntary experiences are not well understood, and have not been imaged selectively. We have used new positron emission tomography (PET) methods(1,2) to study the brain state associated with the occurrence of hallucinations in six schizophrenic patients. Here we present a group study of five patients with classic auditory verbal hallucinations despite medication, demonstrating activations in subcortical nuclei (thalamic, striatal), limbic structures (especially hippocampus), and paralimbic regions (parahippocampal and cingulate gyri, as well as orbito-frontal cortex). We also present a case study of a unique, drug-naive patient with visual as well as auditory verbal hallucinations, demonstrating activations in visual and auditory/linguistic association cortices as part of a distributed cortical-subcortical network. Activity in deep brain structures, identified with group analysis, may generate or modulate hallucinations, and the particular neocortical regions entrained in individual patients may affect their specific perceptual content. The interaction of these distributed neural systems provides a biological basis for the bizarre reports of schizophrenic patients.

Many neuropsychiatric symptom states are idiosyncratic, involuntary, randomly occurring, subjective, and transient. The brain states associated with these clinically important mental states cannot be imaged directly with existing positron emission tomography (PET) techniques. A new PET method that brings such mental/brain states under experimental control for analysis in single subjects is described. It utilizes a slow bolus H2 15O three-dimensional (3D) regional CBF imaging technique. The analysis focuses upon natural or experimentally induced variance in the temporal distribution of specific neuropsychological events over the course of a study session. For each scan, the amount of radioactivity entering the brain during these events is calculated to derive a score reflecting the contribution of the events to the image. A statistical analysis is then performed to identify those pixels in which the intensity covaries with the scan scores over the subject's scans. This permits the identification of the brain areas associated with the mental state of interest. The method is validated using an auditory sentence-monitoring task. The detection in single subjects of cerebral activations associated with recurrent events as brief as 2 s in duration is demonstrated. This method may be used as a means of imaging ephemeral neurologic or neuropsychiatric symptom states or as an alternative to a subtraction design for activation studies.

We describe the case of a 46-year-old male (SC) who could perform certain rule-induction tasks without awareness of the operative rules after surviving nonaccidental carbon monoxide poisoning. We tested the performance of SC on a series of rule-induction tasks at three stages in his recovery: (I) when he was unable to solve a picture discrimination task, (II) when he could succeed on rules that were based on physical features of the task stimuli (even though he was unable to verbalize these rules), but not on rules that were more abstract in nature, and (III) when he managed to solve both kinds of rules and could verbalize them. The focus of this paper is the differential pattern of performance in the latter two stages. Near-perfect scoring on control tasks suggested that this pattern could not be attributed to either verbal or memory deficits. We offer an explanation in terms of a dissociation between conscious and unconscious modes of information-processing.

Positron emission tomography regional CBF (rCBF) studies of cognitive processes have traditionally required 30-60 mCi of (H2O)-O-15 per scan and intersubject averaging to achieve statistical significance. However, intersubject anatomical, functional, and disease variability can make such an approach problematic. A new method that produces significant results in single subjects is presented. It is based upon high-sensitivity three-dimensional imaging and a ''slow'' bolus administration of < 15 mCi of (H2O)-O-15 per scan. The method is validated in four normal volunteers using control and auditory-language activation tasks with four scans per condition and statistical parametric mapping analysis. It is demonstrated that the rCBF distribution associated with the cognitive state is detected during the arrival of radiotracer in the brain. This occurs over 30 s and constitutes a critical temporal window during which stimulation should be performed. A 90-s acquisition time is found to produce results of greater significance than a 60-s acquisition time. The implications of the results and the functional neuroanatomical findings are discussed. This method is suitable for the study of individual functional neuroanatomy in many neuropsychological, pharmacologic, and symptom states in normal subjects and in patients with psychiatric and neurologic disorders.

A single case of Korsakoff's syndrome, showing classic circumscribed amnesia on traditional neuropsychological tests, performed a number of learning tasks previously used in primates to demonstrate the different anatomical basis of memory systems used to learn about the properties of objects or to learn about rules of responding. The patient (CJ) performed in a manner very similar to lesioned monkeys in that he could learn evaluative tasks (e.g. a red object is nice), but not rule based tasks (e.g. a red object means go left). In consequence CJ learned an object discrimination task in a manner qualitatively different from a group of non-amnesic controls. Although he could not learn rule based tasks, CJ could perform them once he had been given the rule. Detailed analysis of learning showed that CJ could choose the object he had chosen previously, but could not say where it had been or whether he had been rewarded. Furthermore he could recognise a word as familiar, while not remembering its source. We propose that he has a specific impairment in a memory system concerned with the representation of the signification of objects in particular contexts, while representation of the properties of objects remains intact.

It has become increasingly apparent that schizophrenic patients can suffer from many cognitive deficits (Hemsley, 1982). These include a decline in IQ (Nelson et al, 1990), loss of concentration (Garmezy, 1978), and various ‘executive’ difficulties similar to those observed in patients with frontal lobe lesions (Morice, 1990). The availability of a large, population-based sample of schizophrenic patients in the Harrow study provided the opportunity to examine the prevalence of these impairments and to relate them to the signs and symptoms of the disorder.

Pro-opiomelanocortin (POMC) related peptides have been studied in rat tissue and plasma, but they have not been well characterized in the rhesus monkey. Since monkey pituitary may be more similar to the human pituitary than the rat, we have characterized POMC related peptides by immunocytochemical, multiple radioimmunoassays (RIA's) and molecular sieving chromatography. Immunocytochemical staining demonstrated N-acetylated- beta-endorphin (N-Ac- beta-End) and alpha-MSH in a few corticotrophs. RIA's of crude anterior pituitary extract and molecular sieving chromatography demonstrates that the major portion is beta-End sized with a significant proportion being N-acetylated and an alpha-MSH peak. Molecular sieving chromatography of extracted plasma demonstrated a similar pattern to that seen in the anterior pituitary. These data suggest that rhesus monkey processes POMC differently than rat or man.

The sedimentation velocity and molecular weight characteristics of ovine follicle-stimulating hormone have been studied in relation to their dependence on buffer pH and protein concentration. Apparent sedimentation coefficients are shown to be a function of protein concentration and buffer pH. The calculated s°20,w values are 3.13, 3.50, 2.86 and 2.12 in buffers of pH 7.0, 5.0, 4.2 and 3.2, respectively. Weight average molecular weights as determined by sedimentation equilibrium techniques are also pH- and concentration dependent. The apparent weight average molecular weight decreases from 39 100 at pH 7.0 to 16 800 at pH 3.2. Extrapolation of apparent molecular weight to zero protein concentration yields a true molecular weight of 35 700 in a buffer system of pH 5.0.