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Aim: Difficulties in social functioning have been observed in youth at clinical high-risk (CHR) of psychosis even in those who do not go on to develop a psychotic illness. Few treatment studies have attempted to improve social functioning in this population. The aim of this study was to conduct a randomized trial comparing the effects of Cognitive-Behavioral Social Skills Training (CBSST) with a supportive therapy (ST)., Methods: Both CBSST and ST were weekly group therapies, delivered over 18 weeks. This was a 2-arm trial with single-blinded ratings and intention-to-treat analyses. Assessments occurred at baseline, end-of-treatment, and 12 months after the baseline assessment. The primary outcome was social and role functioning and defeatist performance attitudes were the secondary outcome. Attenuated positive and negative symptoms, anxiety, depression, self-efficacy, and beliefs about self and others were examined as exploratory outcomes., Results: There were no significant differences between the 2 groups at baseline or either of the 2 follow-ups. However, at follow-ups, in each group there were significant improvements in clinical symptoms. These could not be attributed to group treatment since there was no control or wait-list group., Conclusions: Since poor social functioning is one of the most observed difficulties in CHR individuals, and a decline in social functioning may be a significant predictor of later transition to psychosis, future work will be needed to find effective treatments for this decline in functioning for CHR youth., (© The Author(s) 2023. Published by Oxford University Press on behalf of the University of Maryland's school of medicine, Maryland Psychiatric Research Center.)

Objective: Negative symptoms and cognitive impairment in schizophrenia (SZ) remain unmet treatment needs as they are highly prevalent, associated with poor functional outcomes, and resistant to pharmacologic treatment. The current pilot randomized controlled trial examined the efficacy of an integrated Cognitive-Behavioral Social Skills Training and Compensatory Cognitive Training (CBSST-CCT) intervention compared to Goal-focused Supportive Contact (SC) on negative symptoms and cognitive performance., Methods: Fifty-five adults with SZ or schizoaffective disorder with moderate-to-severe negative symptoms were randomized to receive 25 twice-weekly, 1-h manualized group sessions (12.5 weeks total duration) of either CBSST-CCT or SC delivered by master's level clinicians in five community settings. Assessments of negative symptom severity (primary outcomes) and neuropsychological performance, functional capacity, social skills performance, and self-reported functional ability/everyday functioning, psychiatric symptom severity, and motivation (secondary outcomes) were administered at baseline, mid-treatment, post-treatment, and 6-month follow-up., Results: Mixed-effects models using baseline, mid-treatment, and post-treatment data demonstrated significant CBSST-CCT-associated effects on negative symptom severity, as assessed by the Scale for the Assessment of Negative Symptoms (p = .049, r = 0.22), with improvements in diminished motivation driving this effect (p = .037, r = 0.24). The CBSST-CCT group also demonstrated improved verbal learning compared to SC participants (p = .026, r = 0.36). The effects of CBSST-CCT appeared to be durable at 6-month follow-up., Conclusions: CBSST-CCT improved negative symptom severity and verbal learning in high-negative-symptom individuals relative to SC. CBSST-CCT warrants larger investigations to examine its efficacy in treating negative symptoms, along with other symptoms, cognition, and, ultimately, real-world functional outcomes. Clinical Trial registration number NCT02170051., (Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center 2021.)

Sedentary behavior contributes to a shortened life expectancy in individuals with schizophrenia-spectrum disorders (SSDs), highlighting the need for effective interventions to improve health. This study examined whether reduced ecological momentary assessment (EMA) measures of sedentary activities were observed in individuals with SSDs who participated in a 24-week randomized trial of cognitive behavioral social skills training (CBSST) and either intranasal oxytocin or placebo (NCT01752712). Participants ( n = 57) were prompted with EMA surveys seven times per day for seven days during the baseline, 12-week, and 24-week timepoints to sample sedentary behavior ratings, positive and negative affect, interpersonal interactions, and interpersonal interaction appraisals. Results revealed that sedentary behavior and social interactions did not significantly change over the 24-week clinical trial; however, positive and negative affect and defeatist interaction appraisals improved with treatment, and oxytocin produced modest additional improvements in these EMA outcomes. Greater momentary positive affect was significantly associated with greater activity and greater frequency of interactions. Overall, CBSST was effective at improving functioning, momentary affect, and defeatist interaction appraisals, although it did not reduce sedentary behavior; therefore, targeting these factors is not sufficient to reduce sedentary behavior, and adjunct interventions are needed.

Contextual influences on social behavior and affective dynamics are not well understood in schizophrenia. We examined the role of social context on emotions, and the motivation to interact in the future, using dynamic network analysis of ecological momentary assessment (EMA) data. Participants included 105 outpatients with schizophrenia or schizoaffective disorder (SZ) and 76 healthy comparators (HC) who completed 7 days, 7 times a day of EMA. Dynamic networks were constructed using EMA data to visualize causal interactions between emotional states, motivation, and context (e.g., location, social interactions). Models were extended to include the type and frequency of interactions and the motivation to interact in the near future. Results indicated SZ networks were generally similar to HC but that contextual influences on emotion and social motivation were more evident in SZ. Further, feedback loops in HC were likely adaptive (e.g., positive emotions leading to social motivation), but most were likely maladaptive in SZ (e.g., sadness leading to reduced happiness leading to increased sadness). Overall, these findings indicate that network analyses may be useful in specifying emotion regulation problems in SZ and that instability related to contextual influences may be a central aspect of aberrant regulation., (© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Aim: Poor functioning has become a hallmark of many youth at clinical high-risk (CHR) of psychosis. Even for those who do not make the transition to psychosis remain troubled by functional deficits and a decline in functioning increases the odds of transitioning to psychosis. There are very few treatment studies that have attempted to improve social and role functioning. The aim of this paper is to describe the methods of a treatment study to address social and role functioning in CHR., Methods: This was a randomized controlled trial of cognitive-behavioural social skills training (CBSST) versus a supportive therapy. CBSST combines elements of cognitive behaviour therapy (CBT) and social skills training (SST), two evidence-based treatments for schizophrenia. By adding CBT to SST to target functioning outcomes, SST can be used to train new social skills, and thoughts that interfere with skilled performance in the real world can be addressed using CBT. We developed an adapted version of CBSST, more appropriate for the age range and illness severity of typical CHR individuals, to attempt to show improvements in social and role functioning for these young people., Results: Two hundred and three participants were recruited for this study. Results include initial baseline data., Conclusion: This article describes the baseline methodology of a CHR youth who have difficulties in social and/or role functioning. It is one of the first clinical trials to address this significant problem., (© 2021 John Wiley & Sons Australia, Ltd.)

Schizophrenia is a major cause of disability worldwide. As new treatments for functioning are tested, the need grows to demonstrate real-world functioning gains. Ecological momentary assessment (EMA) may provide a more ecologically valid measure of functioning. In this study, smartphone-based EMA was used to signal participants with schizophrenia (N = 100) and controls (N = 71) 7 times a day for 7 days to respond to brief questionnaires about social interactions and functioning behaviors. Excellent adherence was found, with both groups completing an average of 85% of surveys and only 3% of participants with schizophrenia excluded for poor adherence. Four-week test-retest reliability was high (r = .83 for total productive behaviors). Relative to controls, participants with schizophrenia reported significantly less total productive activity (d = 1.2), fewer social interactions (d = 0.3), more nonproductive behaviors (d = 1.0; watching TV, resting), and more time at home (d = 0.8). Within the schizophrenia group, participants living independently showed better functioning on EMA relative to participants in supported housing (d = 0.8) and participants engaged in vocational activities showed better functioning than individuals not engaged in vocational activities (d = 0.55). Modest correlations were found between EMA and an in-lab self-report measure of functioning activities performed in the community, but not between EMA and measures of functional capacity or potential. This study demonstrated the feasibility, sensitivity reliability, and validity of EMA methods to assess functioning in schizophrenia. EMA provides a much-needed measure of what individuals with schizophrenia are actually doing in real-world contexts. These results also suggest that there may be important disjunctions between indices of abilities and actual real-world functioning., (Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center 2019.)

Mobility is an important correlate of physical, cognitive, and mental health in chronic illness, and can be measured passively with mobile phone global positional satellite (GPS) sensors. To date, GPS data have been reported in a few studies of schizophrenia, yet it is unclear whether these data correlate with concurrent momentary reports of location, vary by people with schizophrenia and healthy comparison subjects, or associate with symptom clusters in schizophrenia. A total of 142 participants with schizophrenia ( n  = 86) or healthy comparison subjects ( n  = 56) completed 7 days of ecological momentary assessment (EMA) reports of location and behavior, and simultaneous GPS locations were tracked every five minutes. We found that GPS-derived indicators of average distance travelled overall and distance from home, as well as percent of GPS samples at home were highly correlated with EMA reports of location at the day- and week-averaged level. GPS-based mobility indicators were lower in schizophrenia with medium to large effect sizes. Less GPS mobility was related to greater negative symptom severity, particularly diminished motivation, whereas greater GPS mobility was weakly associated with more community functioning. Neurocognition, depression, and positive symptoms were not associated with mobility indicators. Therefore, passive GPS sensing could provide a low-burden proxy measure of important outcomes in schizophrenia, including negative symptoms and possibly of functioning. As such, passive GPS sensing could be used for monitoring and timely interventions for negative symptoms in young persons at high risk for schizophrenia., Competing Interests: Competing interestsDr. Harvey has received consulting fees or travel reimbursements from Allergan, Alkermes, Akili, Biogen, Boehringer Ingelheim, Forum Pharma, Genentech (Roche Pharma), Intra-Cellular Therapies, Jazz Pharma, Lundbeck Pharma, Minerva Pharma, Otsuka America (Otsuka Digital Health), Sanofi Pharma, Sunovion Pharma, Takeda Pharma, and Teva. He receives royalties from the Brief Assessment of Cognition in Schizophrenia and the MATRICS Consensus Battery. He is chief scientific officer of i-Function, Inc. He has a research grant from Takeda and from the Stanley Medical Research Foundation. Dr. Granholm has received consulting fees from Otsuka Pharmaceuticals. The remaining authors declare no competing interests., (© The Author(s) 2019.)

Background: Individuals with schizophrenia have deficits in social cognition that are associated with poor functional outcome. Unfortunately, current treatments result in only modest improvement in social cognition. Oxytocin, a neuropeptide with pro-social effects, has significant benefits for social cognition in the general population. However, studies examining the efficacy of oxytocin in schizophrenia have yielded inconsistent results. One reason for inconsistency may be that oxytocin has typically not been combined with psychosocial interventions. It may be necessary for individuals with schizophrenia to receive concurrent psychosocial treatment while taking oxytocin to have the context needed to make gains in social cognitive skills., Methods: The current study tested this hypothesis in a 24-week (48 session) double-blind, placebo-controlled trial that combined oxytocin and Cognitive-Behavioral Social Skills Training (CBSST), which included elements from Social Cognition and Interaction Training (SCIT). Participants included 62 outpatients diagnosed with schizophrenia (placebo n = 31; oxytocin n = 31) who received 36 IU BID, with supervised administration 45 min prior to sessions on CBSST group therapy days. Participants completed a battery of measures administered at 0, 12, and 24 weeks that assessed social cognition., Results: CBSST generally failed to enhance social cognition from baseline to end of study, and there was no additive benefit of oxytocin beyond the effects of CBSST alone., Conclusions: Findings suggest that combined CBSST and oxytocin had minimal benefit for social cognition, adding to the growing literature indicating null effects of oxytocin in multi-dose trials. Methodological and biological factors may contribute to inconsistent results across studies.

Neurocognitive and theory of mind deficits, dysfunctional attitudes, and negative symptoms have all been linked to poor functioning in schizophrenia, but interactions among these factors have not been extensively examined. We investigated whether dysfunctional attitudes (e.g., defeatist performance beliefs and social disinterest attitudes) moderated associations between neurocognition and theory of mind and poor everyday functioning and social competence in 146 participants with schizophrenia. We examined whether cognitive deficits are more likely to influence functioning in participants with more severe dysfunctional attitudes. Social disinterest, but not defeatist performance, attitudes were found to moderate associations between cognitive deficits and social competence but not everyday functioning, such that neurocognition and theory of mind deficits were only associated with poorer social competence in participants with more severe social disinterest attitudes. In contrast, no significant moderation effects were found for defeatist performance beliefs. Findings indicate that deficits in abilities were less likely to impact social competence in participants with greater interest in socializing. It may be that greater motivation for socializing engenders increased practice and engagement in social interactions, which then leads to greater social competence despite poor cognitive abilities. Treatments that target social disinterest attitudes may lead to greater social competence and engagement., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: We assessed the efficacy and tolerability of 5 low-volume bowel preparations for colonoscopy., Study: We performed an investigator-blinded, randomized trial of 5 bowel preparations: 64 ounces of Gatorade and 306 or 357 g of PEG, both given the day prior; Gatorade and 306 g PEG, 2 L PEG-electrolyte solution with ascorbic acid, and sulfate solution, all 3 given as a split dose. One thousand outpatients consumed their preparation before a morning colonoscopy. The primary endpoint was colon cleanliness assessed by the Chicago Bowel Preparation Scale (BPS). Tolerability was assessed using a subject questionnaire. Another primary endpoint was patient acceptance of a split-dose bowel preparation assessed using a subject questionnaire., Results: No statistically significant differences in the modified Chicago BPS were found among Gatorade and 357 g of PEG given as a day-prior dose and the 3 split-dose arms with 98.5% of colons cleansed adequately. The Gatorade and 357 g of PEG had significantly lower Chicago BPS fluid scores and Chicago BPS total scores (indicating dryer colons that required more irrigation) than the 3 split-dose arms. The Gatorade and PEG preparations were better tolerated. Many subjects are unwilling to consume a split-dose preparation and the majority of subjects would prefer a day-prior preparation with this preference highly dependent on the type of preparation they just consumed., Conclusions: The cleanliness of the colons was not significantly different among the 3 split-dose preparations. Day-prior dosing of Gatorade and 357 g of PEG allowed the mucosa to be visualized as well as did the split-dose preparations.

Despite the increasing attention to social appraisals in suicide risk, the interpersonal correlates of suicidal thoughts and behavior in schizophrenia are not well understood. Ecological momentary assessment could reveal whether dysfunctional social appraisals and behavior are evident in people with schizophrenia with suicidal ideation. A total of 93 outpatients with diagnoses of schizophrenia with (n=18, 19%) and without (N=75; 81%) suicidal ideation participated in one week of intensive daily monitoring via mobile devices, generating real-time reports on the quantity of social interactions and appraisals about them, as well as information concerning concurrent affect and symptoms. The presence of suicidal ideation was not associated with the quantity of social interactions or time spent alone, but it was associated with the anticipation of being alone as well as greater negative and lower positive affect when alone. Despite this aversive experience of being alone, people with suicidal ideation reported negative appraisals about the value of recent and potential social interactions. These findings suggest that suicidal ideation in schizophrenia may not be associated with the quantity of social interactions, but with negative expectations about the quality of social interactions coupled with an aversive experience of being alone. Cognitive therapy interventions that address negative expectations and pleasure about social interactions, especially when alone, may reduce suicidal ideation., (Copyright © 2016. Published by Elsevier B.V.)

Background: Schizophrenia leads to profound disability in everyday functioning (e.g., difficulty finding and maintaining employment, housing, and personal relationships). Medications can effectively reduce positive symptoms (e.g., hallucinations and delusions), but they do not meaningfully improve daily life functioning. Psychosocial evidence-based practices (EBPs) improve functioning, but these EBPs are not available to most people with schizophrenia. The field must close the research and service delivery gap by adapting EBPs for schizophrenia to facilitate widespread implementation in community settings. Our hybrid effectiveness and implementation study represents an initiative to bridge this divide. In this study we will test whether an existing EBP (i.e., Cognitive Behavioral Social Skills Training (CBSST)) modified to work in practice settings (i.e., Assertive Community Treatment (ACT) teams) commonly available to persons with schizophrenia results in better consumer outcomes. We will also identify key factors relevant to developing future CBSST implementation strategies., Methods/design: For the effectiveness study component, persons with schizophrenia will be recruited from existing publicly funded ACT teams operating in community settings. Participants will be randomized to one of the 2 treatments (ACT alone or ACT + Adapted CBSST) and followed longitudinally for 18 months with assessments every 18 weeks after baseline (5 in total). The primary outcome domain is psychosocial functioning (e.g., everyday living skills and activities related to employment, education, and housing) as measured by self-report, testing, and observation. Additional outcome domains of interest include mediators of change in functioning, symptoms, and quality of services. Primary analyses will be conducted using linear mixed-effects models for continuous data. The implementation study component consists of a structured, mixed qualitative-quantitative methodology (i.e., Concept Mapping) to characterize and assess the implementation experience from multiple stakeholder perspectives in order to inform future implementation initiatives., Discussion: Adapting CBSST to fit into the ACT service delivery context found throughout the United States creates an opportunity to substantially increase the number of persons with schizophrenia who could have access to and benefit from EBPs. As part of the implementation learning process training materials and treatment workbooks have been revised to promote easier use of CBSST in the context of brief community-based ACT visits., Trial Registration: ClinicalTrials.gov NCT02254733 . Date of registration: 25 April 2014.

Objectives: Current bowel preparation scales (BPSs) have significant limitations including an inability to distinguish among bowel preparations that adequately cleanse a high percentage of colons. We assessed the reliability and validity of the new Chicago BPS and compared it with existing BPSs., Methods: We performed a prospective evaluation of the cleanliness of 150 colons. Inter-rater agreement was assessed using kappa and Pearson correlation coefficients. Each colon was rated by a gastroenterologist and physician's assistant using the Ottawa BPS, the Boston BPS, a dichotomous (adequate/inadequate) BPS (where adequate was defined as being able to visualize at least 95% of the mucosa), and the Chicago BPS., Results: Pearson correlation coefficients between the gastroenterologists and physician's assistant for total BPS scores were 0.79 (95% confidence interval (CI): 0.73, 0.85), 0.79 (95% CI: 0.72, 0.84), and 0.84 (95% CI: 0.79, 0.88) for the Ottawa, Boston, and Chicago BPSs, respectively. Kappa coefficients for right, middle, and distal colon segment ratings were 0.66, 0.53, and 0.49, respectively, for the Ottawa BPS; 0.64, 0.66, and 0.54, respectively, for the Boston BPS; and 0.70, 0.62, and 0.63, respectively, for the Chicago BPS. Differences between the Chicago BPS and the other BPSs were not statistically significant. The Chicago BPS exhibited the best correspondence between BPS total score and the adequate/inadequate BPS., Conclusions: This study demonstrated the validity and reliability of the Chicago BPS. The better defined grading criteria, better designed numerical ratings scale, and better correspondence between Chicago BPS total score and the adequate/inadequate BPS make the Chicago BPS an attractive alternative to the Ottawa BPS and the Boston BPS.

Objectives: We assessed the safety, efficacy, and tolerability of a new preparation of Gatorade and polyethylene glycol (PEG) for colonoscopy with or without bisacodyl compared with NuLYTELY., Methods: We performed an investigator-blinded, placebo-controlled, randomized trial of 64 oz of Gatorade and 306 g of PEG (G/PEG) with or without 10 mg of bisacodyl and NuLYTELY. A total of 600 outpatients consumed their preparation the day before a morning colonoscopy. The primary endpoint was colon cleanliness assessed by the Boston Bowel Preparation Scale (BBPS). Tolerability was assessed using a subject questionnaire, and safety was assessed from a basic metabolic profile drawn before the colonoscopy., Results: Adding bisacodyl to G/PEG caused more abdominal bloating/cramps (P<0.01) and did not result in a cleaner colon (P=0.66) compared with G/PEG without bisacodyl. The BBPS scores in both the G/PEG arms and NuLYTELY arm were not significantly different (P=0.19). Compared with subjects in the NuLYTELY arm, subjects in the G/PEG without bisacodyl arm had less nausea (P<0.04), vomiting (P<0.02), abdominal pain (P<0.02), bloating (P<0.005), difficulty drinking the liquid (P<0.0001), and found the overall preparation easier to tolerate (P<0.0001). Subjects in the combined G/PEG arms had a lower serum sodium (P<0.0007), chloride (P<0.007), and BUN (P<0.0001) levels than those in the NuLYTELY arm, but this did not cause any clinical symptoms., Conclusions: Bisacodyl added to G/PEG for colon lavage caused more side effects and did not result in a cleaner colon. The G/PEG preparations cleansed the colon as well as NuLYTELY, were far better tolerated, and were equally safe.

Mobile Assessment and Treatment for Schizophrenia (MATS) employs ambulatory monitoring methods and cognitive behavioral therapy interventions to assess and improve outcomes in consumers with schizophrenia through mobile phone text messaging. Three MATS interventions were developed to target medication adherence, socialization, and auditory hallucinations. Participants received up to 840 text messages over a 12-week intervention period. Fifty-five consumers with schizophrenia or schizoaffective disorder were enrolled, but 13 consumers with more severe negative symptoms, lower functioning, and lower premorbid IQ did not complete the intervention, despite repeated prompting and training. For completers, the average valid response rate for 216 outcome assessment questions over the 12-week period was 86%, and 86% of phones were returned undamaged. Medication adherence improved significantly, but only for individuals who were living independently. Number of social interactions increased significantly and a significant reduction in severity of hallucinations was found. In addition, the probability of endorsing attitudes that could interfere with improvement in these outcomes was also significantly reduced in MATS. Lab-based assessments of more general symptoms and functioning did not change significantly. This pilot study demonstrated that low-intensity text-messaging interventions like MATS are feasible and effective interventions to improve several important outcomes, especially for higher functioning consumers with schizophrenia.

The finished sequence of human chromosome 20 comprises 59,187,298 base pairs (bp) and represents 99.4% of the euchromatic DNA. A single contig of 26 megabases (Mb) spans the entire short arm, and five contigs separated by gaps totalling 320 kb span the long arm of this metacentric chromosome. An additional 234,339 bp of sequence has been determined within the pericentromeric region of the long arm. We annotated 727 genes and 168 pseudogenes in the sequence. About 64% of these genes have a 5' and a 3' untranslated region and a complete open reading frame. Comparative analysis of the sequence of chromosome 20 to whole-genome shotgun-sequence data of two other vertebrates, the mouse Mus musculus and the puffer fish Tetraodon nigroviridis, provides an independent measure of the efficiency of gene annotation, and indicates that this analysis may account for more than 95% of all coding exons and almost all genes.

The human genome is by far the largest genome to be sequenced, and its size and complexity present many challenges for sequence assembly. The International Human Genome Sequencing Consortium constructed a map of the whole genome to enable the selection of clones for sequencing and for the accurate assembly of the genome sequence. Here we report the construction of the whole-genome bacterial artificial chromosome (BAC) map and its integration with previous landmark maps and information from mapping efforts focused on specific chromosomal regions. We also describe the integration of sequence data with the map.

We constructed maps for eight chromosomes (1, 6, 9, 10, 13, 20, X and (previously) 22), representing one-third of the genome, by building landmark maps, isolating bacterial clones and assembling contigs. By this approach, we could establish the long-range organization of the maps early in the project, and all contig extension, gap closure and problem-solving was simplified by containment within local regions. The maps currently represent more than 94% of the euchromatic (gene-containing) regions of these chromosomes in 176 contigs, and contain 96% of the chromosome-specific markers in the human gene map. By measuring the remaining gaps, we can assess chromosome length and coverage in sequenced clones.

Deletion of the long arm of chromosome 20 represents the most common chromosomal abnormality associated with the myeloproliferative disorders (MPDs) and is also found in other myeloid malignancies including myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML). Previous studies have identified a common deleted region (CDR) spanning approximately 8 Mb. We have now used G-banding, FISH or microsatellite PCR to analyse 113 patients with a 20q deletion associated with a myeloid malignancy. Our results define a new MPD CDR of 2.7 Mb, an MDS/AML CDR of 2.6 Mb and a combined 'myeloid' CDR of 1.7 Mb. We have also constructed the most detailed physical map of this region to date--a bacterial clone map spanning 5 Mb of the chromosome which contains 456 bacterial clones and 202 DNA markers. Fifty-one expressed sequences were localized within this contig of which 37 lie within the MPD CDR and 20 within the MDS/AML CDR. Of the 16 expressed sequences (six genes and 10 unique ESTs) within the 'myeloid' CDR, five were expressed in both normal bone marrow and purified CD34 positive cells. These data identify a set of genes which are both positional and expression candidates for the target gene(s) on 20q.

An automated image analysis (IA) technique has been developed to obtain a measure of the amount (i.e. number and area) of gunshot residue (GSR) particles within and around a gunshot wound. Sample preparation and IA procedures were standardised to improve the reproducibility of the IA measurements of GSR. Measurements of GSR from test firings into goat hide were enhanced by staining the barium and lead components present on the skin sections with Alizarin Red S. The amount of GSR detected on the stained skin sections was compared with backscatter electron micrographs of the same sections. The differences were deemed to be insignificant when the variability in the repeated test firings were taken into consideration. Preliminary results indicated that the decreasing relationship between firing range and the amount of GSR deposited was non-linear, and that for firing ranges of up to 20 cm the amount of GSR deposited from repeated shots fired from the same distance was highly variable.

A statistical investigation of the relationship between firing range and the amount and distribution of gunshot residue (GSR), used automated image analysis (IA) to quantify GSR deposit resulting from firings into pig skin, from distances ranging between contact and 45 cm. Overall, for a Ruger .22 semi-automatic rifle using CCI solid point, high velocity ammunition, the total area of GSR deposit on the skin sections decreased in a non-linear fashion with firing range. More specifically there were significant differences in the amount of GSR deposited from shots fired at contact compared with shots fired from distances between 2.5 and 45 cm; and between shots fired from a distance of 20 cm or less, with shots fired at a distance of 30 cm or more. In addition, GSR particles were heavily concentrated in the wound tract only for contact and close range shots at 2.5 cm, while the particle distribution was more uniform between the wound tract and the skin surfaces for shots fired from distances greater than 2.5 cm. Consequently, for future scientific investigations of gunshot fatalities, once standards have been established for the weapon and ammunition type in question, image analysis quantification of GSR deposited in and around the gunshot wound may be capable of providing a reliable, statistical basis for estimating firing range.

This X-ray diffraction (XRD) investigation of heat-treated human femoral bone showed that the main mineral phase of both unheated bone and bone heated to 600 degrees C resembled that of a poorly crystalline form of hydroxyapatite. The rod-shaped apatite crystals in unheated bone persisted in bone heated up to 400 degrees C. Recrystallization at approximately 600 degrees C, produced larger crystals, which either retained their original morphology or changed to tabular or equidimensional shapes. The size of the apatite crystals in unheated and heated bone specimens was dependent on both temperature and age. When heated above 600 degrees C the crystallinity of the bone mineral increased, and the XRD pattern more closely resembled that of hydroxyapatite. Partial decomposition of the hydroxyapatite phase to calcium oxide above 1000 degrees C, and beta-tricalcium phosphate, alpha-tricalcium phosphate, and calcium oxide phosphate between 1200 degrees C and 1400 degrees C, indicated that the original apatite phase was both calcium deficient and contained carbonate. The relative peak intensities of the thermal decomposition products were related to some extent to the age of the deceased person and reflected the compositional changes that occur during bone aging. Because the thermally induced changes to the composition and ultrastructure of bone mineral were influenced by the age of the individual, this investigation proposed that the heat treatment of bone tissue may offer an alternative way of studying bone aging.

This report describes the heat-induced alterations in human bone tissue observed using scanning electron microscopy and microradiography. Femoral bone samples were taken from persons varying in age from 1 year to 97 years at the time of their death. The bone was heated at selected temperatures in the range 200-1600 degrees C for periods of 2, 12, 18 and 24 h. Macroscopically, changes in colour occurred, together with some shrinkage, fracturing and distortion. However, dramatic changes occurred at the ultrastructural level. These changes included the progressive combustion of the organic portion of the bone tissue up to 400 degrees C and recrystallisation of the bone mineral beginning at 600 degrees C. Recrystallisation produced a range of crystal morphologies: spherical, hexagonal, platelets, rosettes and irregular. Crystal growth occurred at temperatures > 600 degrees C. Sintering led to fusion of crystals at 1000 degrees C. This process continued up to temperatures > 1400 degrees C. At 1600 degrees C the bone mineral melted. On heating, the morphology of crystals formed, and the ultrastructural changes which occurred, were found to be related to the age of the deceased, the temperature to which the bone had been heated and the duration of heating. These results are of importance to forensic scientists, arson investigators and paleoarcheologists in their investigation of cremated human bones, particularly when only fragments of bone are available, in order to determine something of the life history of the deceased and the circumstances surrounding the death.

Fragments of the incinerated remains of a fire victim were studied using scanning electron microscopy and microradiography. These observations were then compared with the heat-induced alterations found in laboratory heat-treated human bone. The incinerated bone fragments exhibited a range of colours, including black, grey and white, concomitant with alterations to the ultrastructure and microstructure of the bone tissue. The colour of the incinerated bone tissue, and the crystal habit and size associated with each region of colour, indicated a gradual decrease in the temperature attained in the bone, as a function of the radial distance from the outer cortical bone surface. A maximum temperature in the range approximately 1000-1200 degrees C had been attained in the outer cortical bone regions that were white in colour. A minimum temperature of 300 degrees C had been attained in the inner cortical bone regions that were black in colour. The period of time over which the fire attained the maximum temperature was inferred to be too short for the bone tissue to have reached an equilibrium with the surrounding environment, as the fire was due to a sudden ignition. However, the minimum temperature recorded was attained for a longer period of time as the organic contents of the Haversian canals and the medullary cavity had been completely combusted. From examinations of the spherical-type crystal size in the grey regions of cortical bone, the habit of the hexagonal-type crystals in the white regions of bone, and the preferred orientation of the mineralised collagen fibrils in the Haversian canals situated in the black regions of cortical bone, it was suggested that the deceased person was a young-to-mature adult, possibly aged 20-40 years.

The tropical marine sponge Amphimedon terpenensis (family Niphatidae, order Haplosclerida) has previously been shown to possess unusual lipids, including unusual fatty acids. The biosynthetic origin of these fatty acids is of interest as the sponge supports a significant population of eubacterial and cyanobacterial symbionts. The total fatty acid composition of the sponge was analyzed by gas chromatography/mass spectrometry of the methyl esters. Among the most abundant of the fatty acids in intact tissue were 16:0, 18:0 and 3,7,11,15-tetramethyl-hexadecanoic (phytanic) acid. In addition, three brominated fatty acids, (5E,9Z)-6-bromo-5,9-tetracosadienoic acid (24:2Br), (5E,9Z)-6-bromo-5,9-pentacosadienoic acid (25:2Br) and (5E,9Z)-6-bromo-5,9-hexacosadienoic acid (26:2Br) were also present. The three brominated fatty acids, together with phytanic acid, were isolated from both ectosomal (superficial) and choanosomal (internal) regions of the sponge. Analysis of extracts prepared from sponge/symbiont cells, partitioned by density gradient centrifugation on Ficoll, indicated that phytanic acid and the three brominated fatty acids were associated with sponge cells only. Further, a fatty acid methyl ester sample from intact tissue of A. terpenensis was partitioned according to phospholipid class, and the brominated fatty acids were shown to be associated with the phosphatidylserine and phosphatidylethanolamine fractions that are commonly present in marine sponge lipids. The phosphatidylcholine and phosphatidylglycerol fractions were rich in the relatively shorter chain fatty acids (16:0 and 18:0). The association of brominated long-chain fatty acids (LCFA) with sponge cells has been confirmed. The findings allow comment on the use of fatty acid profiles in chemotaxonomy and permit further interpretation of LCFA biosynthetic pathways in sponges.(ABSTRACT TRUNCATED AT 250 WORDS)

The Rsr1 protein of Saccharomyces cerevisiae has been shown to be essential for bud site selection (Bender, A., and Pringle, J. (1989) Proc. Natl. Acad. Sci. U.S.A. 86, 9976-9980). This protein of 272 amino acids shares approximately 50% sequence identity with both Ras and Rap GTPases. However, neither GTP binding nor GTPase activity of the Rsr1 protein has been reported. The Rsr1 protein shares with human Rap1 GTPases the four specific motifs, i.e. Gly-12, residues 32-40, Ala-59, and residues 64-70, that are required for GAP3-dependent activation of the Rap1 GTPases. In this paper we demonstrate that the intrinsic GTPase activity of the Rsr1 protein is stimulated by GAP3 purified from bovine brain cytosol. The Rsr1 GTPase is not activated by either GAP1 or GAP2 which are specific for the Ras and Rho GTPases, respectively. Thus, it appears that the Rsr1 GTPase is a new member of the Rap1 GTPase family. Replacement of Gly-12 by Val in the Rsr1 GTPase completely abolishes the GAP3-dependent activation. The chimeric GTPases, Ras(1-60)/Rsr1(61-168) and Rsr1(1-65)/Ras(66-189), are activated by GAP3 but not by GAP1. Replacement of Thr-65 by Ser in the latter chimeric GTPase completely abolishes the GAP3-dependent activation, indicating that Thr-65 is required for distinguishing GAP3 from GAP1. We have previously shown that Gln-61 and Ser-65 are sufficient to determine the GAP1 specificity. Replacement of Thr-35 by Ala in the common effector domain (residues 32-40) of the chimeric Ras/Rsr1 GTPases completely abolishes GAP3-dependent activation.

It has been shown previously that the initial product of mushroom tyrosinase-catalysed oxidation of the monophenol 4-hydroxyanisole (4HA) is 4-methoxy ortho benzoquinone (4-MOB). This study presents evidence that 4-MOB is primarily responsible for the cytotoxicity of 4HA oxidation products in vitro. Equivalent toxicity in a model system was produced by products of tyrosinase catalysed oxidation of 4HA and by synthetic 4-MOB. Cytotoxicity was estimated both by a blebbing assay and by plating efficiency of exposed cells. HPLC analysis of the reaction mixture revealed a positive correlation between cytotoxicity and 4-MOB concentration.

The law of informed consent seeks to actively involve patients in decision making. Most authorities agree that this involvement has not occurred but disagree about why. Some suggest that patients are incapable of understanding medical issues and others that physicians have not explained issues clearly or extensively enough. We observed decision making in several hospital settings and found other significant barriers to patient participation. These barriers include the fact that treatment decisions take place over a long period; there are often many decisions to be made; although patients want information about treatment, they typically believe that decision making is the physician's task; physicians do not understand the rationale for the patient's role in decisions; and the medical decision-making process often involves so many people that the patient does not know who is responsible.

Synchronized cells of the Harding Passey melanoma grown in culture were given a heat shock treatment of 44 degrees C for 36 min. Thymidine incorporation was measured at frequent intervals after heat shock to determine the time of onset of the next DNA synthetic period. If the heat shock was given at the end of G1, the following S was delayed by 20 hr. Heating at other times in the cell cycle resulted in an even longer interval before the onset of S. The end of G1 was also the most resistant to hyperthermic killing and to the effect of heat on the magnitude of thymidine incorporation in the following S. Heating the cells a second time did not repeat the effect of the first treatment unless the second heat shock treatment was at a considerably higher temperature. Thus thermotolerance to heat shock killing also applies to cell-cycle delay.

The human metabolism of 4-hydroxyanisole was investigated by the analysis of urine samples from melanoma patients treated with this substance. The samples were hydrolyzed with glucoronidase and/or arylsulphatase, extracted with ethyl acetate, and, after derivatization with pentafluoropropionylanhydride, analyzed by gas chromatography-mass spectrometry. We were able to identify peaks by their retention times and mass spectra corresponding to 4-hydroxyanisole, 3,4-dihydroxyanisole, and two of its o-methyl derivatives, namely, 3-hydroxy-4-methoxy- and 4-hydroxy-3-methoxyanisole. We also detected a peak of hydroquinone, which may have originated (at least partly) from 4-hydroxyanisole. All the above-mentioned compounds were excreted predominantly as sulphates and glucuronides. Only a small proportion of the substances was present in urine in an unconjugated form. Our results demonstrate that 3,4-dihydroxyanisole is the most important metabolite of 4-hydroxyanisole.

Pancreatic abscess is probably the most serious complication of acute pancreatitis. During the ten-year period from 1966 to 1975, twenty-eight patients with pancreatic abscess following acute pancreatitis were treated by surgical drainage. A review of these cases revealed that there was a lull in the clinical course of the antecedent pancreatitis prior to the time of surgical drainage in 70% of the cases. Despite an aggressive surgical approach, there were major postoperative problems in 26 patients. Sepsis persisted in 14 patients. Major gastrointestinal hemorrhage occurred in seven, intra-abdominal bleeding in nine, and fistulization in 13. Fourteen patients died (a mortality of 50%). The operative treatment of pancreatic abscess must be aggressive and persistent. In addition to extensive drainage with soft sump drains, vigilance must be exercised to avoid pressure against bowel or major vessels. Reoperation should be considered if postoperative improvement is not sustained.