Reducing the risk of criminal exploitation using multi-systemic therapy (the RESET Study): study protocol for a feasibility study and process evaluation.

BACKGROUND: Child criminal exploitation is a form of child abuse that poses a serious risk to the welfare, safety, and wellbeing of young people. Multisystemic therapy (MST) is an intensive family and community-based intervention for young people with anti-social behavioral problems, many of whom will be at risk of criminal exploitation. This protocol describes a pilot feasibility study and process evaluation, designed to examine MST for children at risk of criminal exploitation. METHODS: This pilot feasibility study and process evaluation involves two phases with associated subphases: phase 1.1 involved the collaborative refinement of the logic model adapting MST for children at risk of criminal exploitation; phase 1.2 involved pre-pilot interviews with MST therapists, families, and young people; phase 2.1 is a pilot modeling study of MST for children at risk of criminal exploitation, and; Phase 2.2 is a process evaluation that will involve interviewing stakeholders, MST therapists and employees, families, and young people. The dataset for the process evaluation will include questionnaires completed by parents and young people at baseline, mid-treatment, end of treatment, and 6 months after treatment. We will supplement these data with participant-level data linkage from MST sites and services. RESULTS: Accrual to the pilot stage of this project opened on 6th August 2021 and is due to close on 31st May 2022. We aim to publish the results of this feasibility study and process evaluation in 2023. CONCLUSIONS: The results of this feasibility study and process evaluation will inform the decision as to whether it is advisable to progress to a pilot clinical trial of MST for children at risk of criminal exploitation. TRIAL REGISTRATION: Trial registration: ISRCTN registry, ISRCTN16164816 on 25th January 2021- https://doi.org/10.1186/ISRCTN16164816 .

Types and correlates of school absenteeism among students with intellectual disability.

BACKGROUND: It appears that students with intellectual disability (ID) are more frequently absent from school compared with students without ID. The objective of the current study was to estimate the frequency of absence among students with ID and the reasons for absence. Potential reasons included the attendance problems referred to as school refusal, where absence is related to emotional distress; truancy, where absence is concealed from parents; school exclusion, where absence is instigated by the school; and school withdrawal, where absence is initiated by parents. METHODS: Study participants were 629 parents (84.6% mothers) of Australian school students (Mage  = 11.18 years; 1.8% Aboriginal and/or Torres Strait Islander) with an ID. Participants completed a questionnaire battery that included the School Non-Attendance ChecKlist via which parents indicated the reason their child was absent for each day or half-day absence their child had over the past 20 school days. The absence data presented to parents had been retrieved from school records. RESULTS: Across all students, absence occurred on 7.9% of the past 20 school days. In terms of school attendance problems as defined in existing literature, school withdrawal accounted for 11.1% of absences and school refusal for 5.3% of absences. Students were also absent for other reasons, most commonly illness (32.0%) and appointments (24.2%). Of students with more than one absence (n = 217; 34.5%), about half were absent for more than one reason. Students attending mainstream schools had lower attendance than those attending special schools. CONCLUSIONS: Students with ID were absent for a range of reasons and often for multiple reasons. There were elevated rates of school withdrawal and school refusal. Understanding the reasons for absenteeism can inform targeted prevention and intervention supports.

Social and community inclusion outcomes for adults with autism with and without intellectual disability in Australia.

BACKGROUND: Research suggests that adults with autism tend to have poor outcomes. Outcomes have mostly been defined using summary outcome ratings, with less focus on specific outcomes such as employment, living situation, social satisfaction, loneliness, and friendships. This study aimed to explore social and community outcomes, including employment, education, living arrangements, friendships, and social satisfaction, for autistic adults with and without intellectual disability. METHOD: Eighty-four adults with autism (mean age 34.2 years, SD = 4.5; 67% with co-occurring intellectual disability), recruited as children and adolescents, participated in the current study. Adult social and community inclusion outcomes were explored through interview and questionnaire, both parent/carer-report and self-report. RESULTS: Participants predominantly lived with family or in supported accommodation, did not pursue higher education, and mostly participated in day activity programmes. Most had limited friendships as reported by parents/carers; however, self-report data (n = 28) indicated that adults were largely satisfied with their social relationships. Overall outcome was poor for 57%, and good/very good for 34%. Adults with intellectual disability generally had poorer outcomes. CONCLUSION: Autistic adults encountered numerous difficulties in leading an independent life. Adults with co-occurring intellectual disability were most likely to experience difficulties; however, outcomes ranged from poor to very good for adults without intellectual disability. Discrepancies in parent/carer-report and self-reported experiences of friendships highlight the need to ensure individual experiences are captured in addition to parent/carer-report. Appropriate resources and programmes are crucial for adults with autism to support them to have the choice to live independently.

Coercive parenting: modifiable and nonmodifiable risk factors in parents of children with developmental disabilities.

BACKGROUND: Parents of children with developmental or intellectual disabilities tend to report greater use of coercive parenting practices relative to parents of typically developing children, increasing the risk of adverse child outcomes. However, to date, there is limited research exploring the role and relative contribution of modifiable and nonmodifiable risk factors in parents of children with a disability. The present study aimed to explore the role of various modifiable and nonmodifiable parenting, family and sociodemographic factors associated with the use of coercive parenting practices in parents of children with a disability. METHODS: Caregivers (N = 1392) enrolled in the Mental Health of Young People with Developmental Disabilities (MHYPeDD) programme in Australia completed a cross-sectional survey about their parenting and their child aged 2-12 years with a disability. Measures covered a range of domains including relevant demographic and family background, use of coercive parenting practices, intensity of child behavioural difficulties and questions relating to parent and family functioning such as parental self-efficacy, adjustment difficulties and quality of family relationships. RESULTS: Parents of older children, those who were younger at the birth of their child, and parents who were co-parenting or working reported more use of coercive parenting practices. Greater intensity of child difficulties, poorer parental self-efficacy and parent-child relationships, and more parental adjustment difficulties were also significantly associated with more use of coercive parenting. Examination of the relative contribution of variables revealed parent-child relationship was a key contributing factor, followed by intensity of child behaviour problems, parent adjustment and parent confidence. CONCLUSIONS: These findings highlight a range of factors that should be targeted and modified through upstream prevention programmes and further inform our understanding of how coercive practices may be influenced through targeted parenting interventions.

Participation in sport and physical activity in adults with intellectual disabilities.

BACKGROUND: People with intellectual disability face a number of barriers to participation in physical activity. This paper aimed to determine rates of sport and physical activity participation in an Australian sample of adults with intellectual disability, compared with rates of participation in the general Australian population. A secondary aim was to investigate factors that may contribute to participation of adults with intellectual disability. METHOD: Participants were part of the Australian Child to Adult Development (ACAD) study, consisting of a community sample with intellectual disability (n = 305), groups of adults with autism (n = 94), Down syndrome (n = 64), fragile X syndrome (n = 52), Williams syndrome (n = 45), and Prader-Willi syndrome (n = 30). Participation in sport/physical activity was reported over the past 3 months. Rates of participation were reported for adults with intellectual disability and compared with rates in a general Australian population sample. The relationship between participation in physical activity and age, degree of intellectual disability, physical mobility, living situation, socio-economic disadvantage, and behaviour and emotional problems were also conducted. RESULTS: Participants in the ACAD community sample with intellectual disability participated in sport/physical activity at lower rates than the general Australian population (42% compared with 71%). Having no physical mobility impairment was significantly associated with higher rates of participation. Those with Down syndrome participated in sport/physical activity at higher rates than the community sample with intellectual disability, while no difference in sport/physical activity participation was observed in the groups with autism or other syndromes. CONCLUSION: Australian adults with intellectual disability participate in sport and physical activity at lower rates than the general population. Having a physical mobility impairment was associated with lower rates of participation. However, people living in supported accommodation were more likely to participate than those in other living situations. Having Down syndrome was associated with a higher participation rate than the community sample.

Concurrence of the strengths and difficulties questionnaire and developmental behaviour checklist among children with an intellectual disability.

BACKGROUND: The Strengths and Difficulties Questionnaire (SDQ) is widely used to measure emotional and behavioural problems in typically developing young people, although there is some evidence that it may also be suitable for children with intellectual disability (ID). The Developmental Behaviour Checklist - Parent version (DBC-P) is a measure of emotional and behavioural problems that was specifically designed for children and adolescents with an ID. The DBC-P cut-off has high agreement with clinical diagnosis. The aim of this study was to estimate the relationship between DBC-P and SDQ scores in a sample of children with ID. METHOD: Parents of 83 young people with ID aged 4-17 years completed the parent versions of the SDQ and the DBC-P. We evaluated the concurrent validity of the SDQ and DBC-P total scores, and the agreement between the DBC-P cut-off and the SDQ cut-offs for 'borderline' and 'abnormal' behaviour. RESULTS: The SDQ total difficulties score correlated well with the DBC-P total behaviour problem score. Agreement between the SDQ borderline cut-off and the DBC-P cut-off for abnormality was high (83%), but was lower for the SDQ abnormal cut-off (75%). Positive agreement between the DBC-P and the SDQ borderline cut-off was also high, with the SDQ borderline cut-off identifying 86% of those who met the DBC-P criterion. Negative agreement was weaker, with the SDQ borderline cut-off identifying only 79% of the participants who did not meet the DBC-P cut-off. CONCLUSION: The SDQ borderline cut-off has some validity as a measure of overall levels of behavioural and emotional problems in young people with ID, and may be useful in epidemiological studies that include participants with and without ID. However, where it is important to focus on behavioural profiles in children with ID, a specialised ID instrument with established psychometric properties, such as the DBC-P, may provide more reliable and valid information.

The effects of N-Acetylcysteine on frontostriatal resting-state functional connectivity, withdrawal symptoms and smoking abstinence: A double-blind, placebo-controlled fMRI pilot study.

BACKGROUND: Chronic exposure to drugs of abuse disrupts frontostriatal glutamate transmission, which in turn meditates drug seeking. In animal models, N-Acetylcysteine normalizes dysregulated frontostriatal glutamatergic neurotransmission and prevents reinstated drug seeking; however, the effects of N-Acetylcysteine on human frontostriatal circuitry function and maintaining smoking abstinence is unknown. Thus, the current study tested the hypothesis that N-Acetylcysteine would be associated with stronger frontostriatal resting-state functional connectivity (rsFC), attenuated nicotine withdrawal and would help smokers to maintain abstinence over the study period. METHODS: The present study examined the effects of N-Acetylcysteine on frontostriatal rsFC, nicotine-withdrawal symptoms and maintaining abstinence. Healthy adult, non-treatment seeking smokers (N=16; mean (SD) age 36.5±11.9; cigs/day 15.8±6.1; years/smoking 15.7±8.9) were randomized to a double-blind course of 2400mg N-Acetylcysteine (1200mg b.i.d.) or placebo over the course of 3½ days of monetary-incentivized smoking abstinence. On each abstinent day, measures of mood and craving were collected and participants attended a lab visit in order to assess smoking (i.e., expired-air carbon monoxide [CO]). On day 4, participants underwent fMRI scanning. RESULTS: As compared to placebo (n=8), smokers in the N-Acetylcysteine group (n=8) maintained abstinence, reported less craving and higher positive affect (all p's<.01), and concomitantly exhibited stronger rsFC between ventral striatal nodes, medial prefrontal cortex and precuneus-key default mode network nodes, and the cerebellum [p<.025; FWE]). CONCLUSIONS: Taken together, these findings suggest that N-Acetylcysteine may positively affect dysregulated corticostriatal connectivity, help to restructure reward processing, and help to maintain abstinence immediately following a quit attempt.

Association between adaptive behaviour and age in adults with Down syndrome without dementia: examining the range and severity of adaptive behaviour problems.

BACKGROUND: Studies on adaptive behaviour and ageing in adults with Down syndrome (DS) (without dementia) have typically analysed age-related change in terms of the total item scores on questionnaires. This research extends the literature by investigating whether the age-related changes in adaptive abilities could be differentially attributed to changes in the number or severity (intensity) of behavioural questionnaire items endorsed. METHODS: The Adaptive Behaviour Assessment System-II Adult (ABAS-II Adult) was completed by parents and caregivers of 53 adults with DS aged between 16 and 56 years. Twenty adults with DS and their parents/caregivers were a part of a longitudinal study, which provided two time points of data. In addition 33 adults with DS and their parents/caregivers from a cross-sectional study were included. Random effects regression analyses were used to examine the patterns in item scores associated with ageing. RESULTS: Increasing age was found to be significantly associated with lower adaptive behaviour abilities for all the adaptive behaviour composite scores, expect for the practical composite. These associations were entirely related to fewer ABAS-II Adult items being selected as present for the older participants, as opposed to the scores being attributable to lower item severity. CONCLUSIONS: This study provides evidence for a differential pattern of age-related change for various adaptive behaviour skills in terms of range, but not severity. Possible reasons for this pattern will be discussed. Overall, these findings suggest that adults with DS may benefit from additional support in terms of their social and conceptual abilities as they age.

Outcomes in young adulthood: are we achieving community participation and inclusion?

BACKGROUND: Despite recognition of the importance of integrated community living and support, there is evidence that parents remain the primary caregivers of young adults with intellectual disability (ID). In addition, employment rates remain low in this population. This study aimed to investigate the changes in living arrangements and participation in daytime activities over time in a community population of young people with ID. METHOD: The sample consisted of 536 participants aged 4.0-18.9 years at Wave 1, followed up at Wave 5 when aged 20.5-37.6 years. Information was collected on their living arrangements and daytime activities at both time points, along with living skills and information on community social inclusion at Wave 5. For parents still caring for their adult child with ID, information was also collected on parental ratings of their own mental and physical health, and their satisfaction with the long-term care arrangements for their adult child. RESULTS: A significant proportion of young people were still living with their parents at Wave 5. A greater proportion of those with a severe-profound degree of ID were living in residential care. Parents caring for their adult child reported high levels of mental health problems and dissatisfaction with the long-term care arrangements for their child. A small proportion of young people were in paid employment, and the majority was engaged in structured activities provided for those with an ID. Over one-third of the sample participated in a structured daytime activity for 10 or fewer hours per week, and 7% were not engaged in any structured daytime activity. CONCLUSIONS: These results suggest that adequate provision of accommodation and employment services for young adults with an ID is lacking. In many cases the responsibility of care continues to reside with parents as their children transition from childhood to adulthood. Greater attention is needed to address these issues and facilitate social inclusion and integration for young people with ID.

Behavioural and emotional problems in people with severe and profound intellectual disability.

BACKGROUND: People with severe and profound levels of intellectual disability (ID) are frequently examined as a single group in research. However, these two groups may be significantly different, particularly in the area of emotional and behavioural difficulties. METHOD: The Developmental Behaviour Checklist (DBC) was completed by parents and caregivers of 107 people with severe ID and 22 people with profound ID at four time periods across 12 years. Regression analyses were used to examine trends in sub-scale scores across time and groups. RESULTS: Significant differences between the groups of people with severe and profound ID were found. People with profound ID had significantly lower scores across all sub-scales except Social Relating. This was usually related to fewer items being selected as present for people with profound ID, as opposed to the scores being attributable to lower item severity scores. CONCLUSIONS: There are significant differences between groups of people with severe and profound ID in scores on the DBC, indicating differences in behavioural and emotional problems. Caution should be exercised by researchers treating these two disparate groups as a single group, and by practitioners translating such findings into practice.

Inhibition of colonic motility and defecation by RS-127445 suggests an involvement of the 5-HT2B receptor in rodent large bowel physiology.

BACKGROUND: 5-HT(2B) receptors are localized within the myenteric nervous system, but their functions on motor/sensory neurons are unclear. To explore the role of these receptors, we further characterized the 5-HT(2B) receptor antagonist RS-127445 and studied its effects on peristalsis and defecation. EXPERIMENTAL APPROACH: Although reported as a selective 5-HT(2B) receptor antagonist, any interactions of RS-127445 with 5-HT(4) receptors are unknown; this was examined using the recombinant receptor and Biomolecular Interaction Detection technology. Mouse isolated colon was mounted in tissue baths for isometric recording of neuronal contractions evoked by electrical field stimulation (EFS), or under an intraluminal pressure gradient to induce peristalsis; the effects of RS-127445 on EFS-induced and on peristaltic contractions were measured. Faecal output of rats in grid-bottom cages was measured over 3 h following i.p. RS-127445 and separately, validation of the effective doses was achieved by determining the free, unbound fraction of RS-127445 in blood and brain. KEY RESULTS: RS-127445 (up to 1 micromol x L(-1)) did not interact with the 5-HT(4) receptor. RS-127445 (0.001-1 micromol x L(-1)) did not affect EFS-induced contractions of the colon, although at 10 micromol x L(-1) the contractions were reduced (to 36 +/- 8% of control, n= 4). RS-127445 (0.1-10 micromol x L(-1)) concentration-dependently reduced peristaltic frequency (n= 4). RS-127445 (1-30 mg x kg(-1)), dose-dependently reduced faecal output, reaching significance at 10 and 30 mg x kg(-1) (n= 6-11). In blood and brain, >98% of RS-127445 was protein-bound. CONCLUSIONS AND IMPLICATIONS: High-protein binding of RS-127445 indicates that relatively high doses are required for efficacy. The results suggest that 5-HT(2B) receptors tonically regulate colonic motility.

Screening for autism in young children with developmental delay: an evaluation of the developmental behaviour checklist: early screen.

The ability to identify children who require specialist assessment for the possibility of autism at as early an age as possible has become a growing area of research. A number of measures have been developed as potential screening tools for autism. The reliability and validity of one of these measures for screening for autism in young children with developmental problems was evaluated. The parents of 207 children aged 20-51 months completed the Developmental Checklist-Early Screen (DBC-ES), prior to their child undergoing assessment. Good interrater agreement and internal consistency was found, along with significant correlations with a clinician completed measure of autism symptomatology. High sensitivity was found, with lower specificity for the originally proposed 17-item screening tool and a five-item version.

Pilot study to determine the ability of health-care professionals to undertake drug dose calculations.

BACKGROUND: It is essential for health-care professionals to calculate drug doses accurately. Previous studies have demonstrated that many hospital doctors were unable to accurately convert dilutions (e.g. 1:1000) or percentages (e.g. percentage w/v) of drug concentrations into mass concentrations (e.g. mg/mL). AIMS: The aims of the present study were to evaluate the ability of health-care professionals to perform drug dose calculations accurately and to determine their preferred concentration convention when calculating drug doses. METHODS: A selection of nurses, medical students, house surgeons, registrars and pharmacists undertook a written survey to assess their ability to perform five drug dose calculations. Participants were also asked which concentration convention they preferred when calculating drug doses. The surveys were marked then analysed for health-care professionals as a whole and then by subgroup analysis to assess the performance of each health-care-professional group. RESULTS: Overall, less than 14% of the surveyed health-care professionals could answer all five questions correctly. Subgroup analysis revealed that health-care professionals' ability to calculate drug doses were ranked in the following order: registrars approximately equal to pharmacists > house surgeons > medical students >> nurses. Ninety per cent of health-care professionals preferred to calculate drug doses using the mass concentration convention. CONCLUSIONS: Overall, drug dose calculations were performed poorly. Mass concentration was clearly indicated as the preferred convention for calculating drug doses.

Multiple N-acyl homoserine lactone signals of Rhizobium leguminosarum are synthesized in a distinct temporal pattern.

A common form of bacterial quorum sensing involves the production and release of acyl homoserine lactone (AHL) signal metabolites. The nitrogen-fixing symbiont Rhizobium leguminosarum reportedly produces at least six different AHLs, but little is known about the regulation of biosynthesis of these molecules. We used a radiolabeling protocol to quantify the relative amounts of AHLs synthesized over time by R. leguminosarum cells with and without the symbiosis plasmid pRL1JI. Cells containing pRL1JI were found to produce three predominant signals. In decreasing order of abundance, these were N-(3-oxo)octanoyl homoserine lactone [(3-O)C(8)HSL], N-octanoyl homoserine lactone, and N-hexanoyl homoserine lactone. Cells without pRL1JI produced only two major signals, N-(3-hydroxy-7-cis)tetradecanoyl homoserine lactone [(3-OH)C(14:1)HSL] and (3-O)C(8)HSL. Each AHL exhibited a distinct temporal pattern of synthesis, suggesting that each AHL is subject to unique regulatory mechanisms. While (3-O)C(8)HSL was produced in both cultures, the patterns of synthesis were different in cells with and without pRL1JI, possibly as a result of redundant gene functions that are present on both the chromosome and the symbiosis plasmid. None of the AHLs appeared to regulate its own biosynthesis, although exogenous (3-OH)C(14:1)HSL did activate synthesis of the three AHLs made by cells containing pRL1JI. These results indicate that the synthesis of multiple AHLs in R. leguminosarum is regulated by complex mechanisms that operate independently of quorum sensing itself but that (3-OH)C(14:1)HSL can supersede these controls in pRL1JI-containing cells. This work provides an important global perspective for AHL regulation that both complements and contrasts with the results of previous studies performed with isolated gene systems.

Are there early features of autism in infants and preschool children?

Autism is characterized by impairments in three areas: (i) reciprocal social interaction; (ii) communication; and (iii) repetitive and stereotyped patterns of interest and behaviour. Despite the finding that parents notice abnormalities and problems with their child's development at a very early age, research shows that diagnoses are often made at an age beyond that recommended for the commencement of early intervention. This paper reviews the range of studies that have sought to elucidate the early features of autism in young, preschool children. Impairments in the capacity for reciprocal social interaction involving preverbal, verbal and non-verbal communication, and play and symbolic behaviour are the key features indicative of autism in infants and preschool children.

Extraction of violacein from Chromobacterium violaceum provides a new quantitative bioassay for N-acyl homoserine lactone autoinducers.

Fatty acyl homoserine lactones (AHLs) are used as extracellular quorum sensing signals by a variety of gram-negative bacteria. By activating proteins belonging to the LuxR family of transcriptional regulators, these signal metabolites allow population density-dependent gene regulation within a species, as well as interspecies communication among different bacteria. The experimental detection of AHLs is important in the identification of quorum sensing capabilities in bacteria. Chromobacterium violaceum is a gram-negative bacterium that produces the purple pigment violacein in response to the presence of the AHL N-hexanoyl homoserine lactone (C6HSL). The mini-Tn5 mutant strain C. violaceum CV0blu is deficient in the production of this signal molecule but retains the ability to synthesize violacein in response to the presence of C6HSL and a variety of other short-chain AHLs. We have developed a quantitative bioassay that measures the amount of violacein produced by this strain in response to the presence of different concentrations of various AHL molecules. This new assay provides a means of quantifying the amount of a given AHL present in a bacterial culture and can be used to measure differences in AHL production among different strains or different batch cultures of a given species.

Percutaneous liver biopsy in children: impact of ultrasonography and spring-loaded biopsy needles.

BACKGROUND: Percutaneous liver biopsy is a valued tool of pediatric hepatology. Recent advances in technology have incorporated spring-loaded biopsy needles and ultrasonography in percutaneous liver biopsy. METHODS: To determine the frequency of complications after liver biopsy and whether variables such as needle selections (Jamshidi, Monopty, or ASAP) and ultrasound guidance could predict complications, medical records were retrospectively reviewed of all patients who underwent percutaneous liver biopsy during a 7-year period. Available data were collected from 123 patients who had undergone a total of 249 percutaneous liver biopsies. All patients with evidence of mild clotting abnormalities (8.83%) received platelets, cryoprecipitate, or fresh-frozen plasma. RESULTS: There was a 6.83% incidence of overall complications, and a 2.4% incidence of major complications. The mortality rate was 0.4%. Ultrasound localization did not diminish the risk of bleeding during biopsy. There was no significant difference in the change of hematocrit between the aspiration (Jamshidi) and spring-loaded (Monopty) needles. However, in patients less than 5 years of age, the change of hematocrit was significantly higher (P < 0.05) with the 15- or 18-gauge ASAP needle (Microvasive, Quincy, MA, U.S.A.) than with either the Jamshidi (Allegience Healthcare, Columbia, MD, U.S.A.) or Monopty (Bard Technologies, Covington, GA, U.S.A.) needles. CONCLUSION: Percutaneous liver biopsy is safe, using either aspiration or spring-loaded needles. Ultrasound guidance may not be helpful except in patients who underwent segmental liver transplantation.

The effect of body temperature on myocardial protection conferred by ischaemic preconditioning or the selective adenosine A1 receptor agonist GR79236, in an anaesthetized rabbit model of myocardial ischaemia and reperfusion.

1 The cardioprotective effect of N-[(1S, trans)-2-hydroxycyclopentyl]adenosine (GR79236), an adenosine A1 receptor agonist, was compared with that produced by ischaemic preconditioning in an anaesthetized rabbit model of myocardial ischaemia and reperfusion. In addition, we examined the effect of different body core temperatures on GR79236- or ischaemic preconditioning-induced cardioprotection when administered prior to ischaemia, and on cardioprotection induced by GR79236 administered 10 min prior to the onset of reperfusion. 2 When rabbits were subjected to 30 min occlusion of the left coronary artery, followed by 2 h reperfusion, GR79236 (3 x 10(-8) mol kg-1 i.v. (10.5 microg kg-1 i.v.)) or ischaemic preconditioning (5 min ischaemia followed by 5 min reperfusion), administered or applied 10 min prior to the occlusion, significantly limited the development of infarction. The cardioprotective effect of ischaemic preconditioning was significantly greater than that seen after administration of GR79236. Pre-treatment with the selective adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 3.3 x 10(-6) mol kg-1 (1 mg kg-1 i.v.)), prevented the cardioprotective effect of GR79236, but not that of ischaemic preconditioning. 3 Maintaining body core temperature at 38.5 degrees C rather than at 37.0 degrees C did not influence infarct size in control groups of rabbits, but reduced the cardioprotective effect of GR79236 when administered 10 min prior to occlusion or 10 min prior to the onset of reperfusion. The cardioprotective effect of ischaemic preconditioning was not temperature-dependent. 4 In conclusion, myocardial protection conferred by GR79236 in anaesthetized rabbits is mediated via adenosine A1 receptors. Myocardial protection can be conferred when GR79236 is administered before the onset of ischaemia or reperfusion, and is reduced when body core temperature is maintained at 38.5 degrees C rather than at 37.0 degrees C. In contrast, myocardial protection conferred by ischaemic preconditioning is not reduced by adenosine A1 receptor blockade, or by maintaining body core temperature at 38.5 degrees C rather than at 37.0 degrees C. These findings point to distinct differences in the mechanisms of induction of myocardial protection by adenosine A1 receptor agonist and ischaemic preconditioning. They also highlight the need for careful control of body core temperature when investigating the phenomenon of cardioprotection.

Intercellular communication and group behavior in bacteria.

Group behavior in bacterial populations requires intercellular communication, generally by means of self-produced signals. As the model system of bacterial quorum sensing demonstrates, the integration of these 'group' signals with other global regulators can lead to very complex and sophisticated interactions that are not necessarily limited to the signal-producing species alone.