The Picture Talk Project: Starting a Conversation with Community Leaders on Research with Remote Aboriginal Communities of Australia.

BACKGROUND: Researchers are required to seek consent from Indigenous communities prior to conducting research but there is inadequate information about how Indigenous people understand and become fully engaged with this consent process. Few studies evaluate the preference or understanding of the consent process for research with Indigenous populations. Lack of informed consent can impact on research findings. METHODS: The Picture Talk Project was initiated with senior Aboriginal leaders of the Fitzroy Valley community situated in the far north of Western Australia. Aboriginal people were interviewed about their understanding and experiences of research and consent processes. Transcripts were analysed using NVivo10 software with an integrated method of inductive and deductive coding and based in grounded theory. Local Aboriginal interpreters validated coding. Major themes were defined and supporting quotes sourced. RESULTS: Interviews with Aboriginal leaders (n = 20) were facilitated by a local Aboriginal Community Navigator who could interpret if necessary and provide cultural guidance. Participants were from all four major local language groups of the Fitzroy Valley; aged 31 years and above; and half were male. Themes emerging from these discussions included Research-finding knowledge; Being respectful of Aboriginal people, Working on country, and Being flexible with time; Working together with good communication; Reciprocity-two-way learning; and Reaching consent. CONCLUSION: The project revealed how much more there is to be learned about how research with remote Aboriginal communities should be conducted such that it is both culturally respectful and, importantly, meaningful for participants. We identify important elements in community consultation about research and seeking consent.

The participation of parents of disabled children and young people in health and social care decisions.

BACKGROUND: There is widespread acceptance that parents should be fully involved in decisions about their son or daughter's health and social care. This is reflected in partnership models of practice as well as local and national policy across the United Kingdom. Previous research indicates that parents' experiences of decision making with professionals are mixed. AIM: The research reported here aimed to explore parents' experiences of participating in decisions made with professionals about their disabled son or daughter's care. DESIGN: This research used mixed methods including survey methodology and qualitative in depth interviews. SETTING AND PARTICIPANTS: The research was conducted in one Trust in Northern Ireland. Participants were 77 parents of children and young people with a range of impairments aged between 3 and 28 years. RESULTS: Three themes emerged from the data: taking the lead, not knowing, and getting the balance right. Parents wanted to be involved in all aspects of decision making. Although parents reported many examples of good practice, there were also times when they did not feel listened to or did not have enough information to inform decisions. DISCUSSION AND CONCLUSION: Parents in this research recounted positive as well as negative experiences. Parents took on a protective role when decisions were made about their son or daughter and at times, reported the need to "fight" for their child. The provision of information remains problematic for these families, and at times, this created a barrier to parents' participation in decision making. Partnership approaches to care that recognize parents' expertise are particularly important to parents when decisions are made with professionals.

N-aryl piperazine metabotropic glutamate receptor 5 positive allosteric modulators possess efficacy in preclinical models of NMDA hypofunction and cognitive enhancement.

Impaired transmission through glutamatergic circuits has been postulated to play a role in the underlying pathophysiology of schizophrenia. Furthermore, inhibition of the N-methyl-d-aspartate (NMDA) subtype of ionotropic glutamate receptors (NMDAR) induces a syndrome that recapitulates many of the symptoms observed in patients with schizophrenia. Selective activation of metabotropic glutamate receptor subtype 5 (mGlu5) may provide a novel therapeutic approach for treatment of symptoms associated with schizophrenia through facilitation of transmission through central glutamatergic circuits. Here, we describe the characterization of two novel N-aryl piperazine mGlu5 positive allosteric modulators (PAMs): 2-(4-(2-(benzyloxy)acetyl)piperazin-1-yl)benzonitrile (VU0364289) and 1-(4-(2,4-difluorophenyl)piperazin-1-yl)-2-((4-fluorobenzyl)oxy)ethanone (DPFE). VU0364289 and DPFE induced robust leftward shifts in the glutamate concentration-response curves for Ca(2+) mobilization and extracellular signal-regulated kinases 1 and 2 phosphorylation. Both PAMs displayed micromolar affinity for the common mGlu5 allosteric binding site and high selectivity for mGlu5. VU0364289 and DPFE possessed suitable pharmacokinetic properties for dosing in vivo and produced robust dose-related effects in reversing amphetamine-induced hyperlocomotion, a preclinical model predictive of antipsychotic-like activity. In addition, DPFE enhanced acquisition of contextual fear conditioning in rats and reversed behavioral deficits in a mouse model of NMDAR hypofunction. In contrast, DPFE had no effect on reversing apomorphine-induced disruptions of prepulse inhibition of the acoustic startle reflex. These mGlu5 PAMs also increased monoamine levels in the prefrontal cortex, enhanced performance in a hippocampal-mediated memory task, and elicited changes in electroencephalogram dynamics commensurate with procognitive effects. Collectively, these data support and extend the role for the development of novel mGlu5 PAMs for the treatment of psychosis and cognitive deficits observed in individuals with schizophrenia.

Factors affecting decision making about fertility preservation after cancer diagnosis: a qualitative study.

OBJECTIVE: To increase our understanding of factors underlying the decision to store gametes after the diagnosis of cancer. DESIGN: Qualitative interview study. SETTING: Andrology, Haematology, and Oncology Departments of a Scottish teaching hospital, and patients' own homes. POPULATION: Sixteen men and 18 women aged 17-49 years recently diagnosed with cancer; 15 health professionals concerned in cancer care. METHODS: Audio-recorded semi-structured interviews were transcribed verbatim and analysed thematically. Topics included perceptions of diagnosis; prognosis; future reproductive choices; priorities; quality of information received; communication and decisions made about future reproductive choices; and the role of partners, family, friends and healthcare professionals. Professional interviews examined their role in decision making and that of protocols and guidelines, together with information emerging from patient interview analysis. MAIN OUTCOME MEASURE: Themes identified following analysis of interview transcripts. RESULTS: The primary barriers to pursuing fertility preservation were the way in which information was provided and the 'urgent need for treatment' conveyed by staff. Survival was always viewed as paramount, with future fertility secondary. Sperm banking was viewed as 'part and parcel' of oncology care, and the majority of men quickly stored sperm as 'insurance' against future infertility. Few women were afforded the opportunity to discuss their options, reflecting clinicians' reservations about the experimental nature of egg and ovarian tissue cryopreservation, and the need for partner involvement in embryo storage. CONCLUSIONS: Significant gaps in the information provided to young women diagnosed with cancer suggest the need for an early appointment with a fertility expert.

Mitochondria-dependent and -independent regulation of Granzyme B-induced apoptosis.

Granzyme B (GraB) is required for the efficient activation of apoptosis by cytotoxic T lymphocytes and natural killer cells. We find that GraB and perforin induce severe mitochondrial perturbation as evidenced by the release of cytochrome c into the cytosol and suppression of transmembrane potential (Deltapsi). The earliest mitochondrial event was the release of cytochrome c, which occurred at the same time as caspase 3 processing and consistently before the activation of apoptosis. Granzyme K/perforin or perforin treatment, both of which kill target cells efficiently but are poor activators of apoptosis in short-term assays, did not induce rapid cytochrome c release. However, they suppressed Deltapsi and increased reactive oxygen species generation, indicating that mitochondrial dysfunction is also associated with this nonapoptotic cell death. Pretreatment with peptide caspase inhibitors zVAD-FMK or YVAD-CHO prevented GraB apoptosis and cytochrome c release, whereas DEVD-CHO blocked apoptosis but did not prevent cytochrome c release, indicating that caspases act both up- and downstream of mitochondria. Of additional interest, Deltapsi suppression mediated by GraK or GraB and perforin was not affected by zVAD-FMK and thus was caspase independent. Overexpression of Bcl-2 and Bcl-XL suppressed caspase activation, mitochondrial cytochrome c release, Deltapsi suppression, and apoptosis and cell death induced by GraB, GraK, or perforin. In an in vitro cell free system, GraB activates nuclear apoptosis in S-100 cytosol at high doses, however the addition of mitochondria amplified GraB activity over 15-fold. GraB- induced caspase 3 processing to p17 in S-100 cytosol was increased only threefold in the presence of mitochondria, suggesting that another caspase(s) participates in the mitochondrial amplification of GraB apoptosis. We conclude that GraB-induced apoptosis is highly amplified by mitochondria in a caspase-dependent manner but that GraB can also initiate caspase 3 processing and apoptosis in the absence of mitochondria.

YB-1 DNA-binding protein represses interferon gamma activation of class II major histocompatibility complex genes.

Interferon gamma (IFN-gamma) is the most potent inducer of class II major histocompatibility complex (MHC) genes. This induction is uniquely mediated by three DNA elements in the promoter region of class II MHC genes. One of these DNA elements, Y, contains an inverted CCAAT box. Previously, we have screened a lambda gt11 library for Y-binding proteins and identified the YB-1 gene. Here we provide evidence that YB-1 can repress the IFN-gamma induction of class II MHC promoter as well as the Invariant chain (Ii) gene which also contains a Y element in its promoter. This was demonstrated by cotransfecting a YB-1 expression vector with promoter-reporter gene constructs. As an alternate approach, an efficient transient transfection system was developed which resulted in a > 70% transfection efficiency. Transfection of YB-1 by this procedure resulted in the near abrogation of IFN-gamma induced HLA-DR antigen and mRNA expression. These findings show the functional suppression of class II MHC gene induction by the YB-1 protein.

Expression of a dominant negative mutant of interleukin-1 beta converting enzyme in transgenic mice prevents neuronal cell death induced by trophic factor withdrawal and ischemic brain injury.

To explore the role of the interleukin (IL)-1 beta converting enzyme (ICE) in neuronal apoptosis, we designed a mutant ICE gene (C285G) that acts as a dominant negative ICE inhibitor. Microinjection of the mutant ICE gene into embryonal chicken dorsal root ganglial neurons inhibits trophic factor withdrawal-induced apoptosis. Transgenic mice expressing the fused mutant ICE-lacZ gene under the control of the neuron specific enolase promoter appeared neurologically normal. These mice are deficient in processing pro-IL-1 beta, indicating that mutant ICEC285G blocks ICE function. Dorsal root ganglial neurons isolated from transgenic mice were resistant to trophic factor withdrawal-induced apoptosis. In addition, the neurons isolated from newborn ICE knockout mice are similarly resistant to trophic factor withdrawal-induced apoptosis. After permanent focal ischemia by middle cerebral artery occlusion, the mutant ICEC285G transgenic mice show significantly reduced brain injury as well as less behavioral deficits when compared to the wild-type controls. Since ICE is the only enzyme with IL-1 beta convertase activity in mice, our data indicates that the mutant ICEC285G inhibits ICE, and hence mature IL-1 beta production, and through this mechanism, at least in part, inhibits apoptosis. Our data suggest that genetic manipulation using ICE family dominant negative inhibitors can ameliorate the extent of ischemia-induced brain injury and preserve neurological function.

Global warming and the Arctic: a new world beyond the reach of the Grinnellian niche?

The levels of CO(2) in the atmosphere have already far exceeded values attained at any other time over at least the past 650,000 years. Temperature increases due to rising greenhouse gases will be amplified in Arctic and subarctic regions, and winter warming will be enhanced relative to summer warming. Climate in large areas of high latitudes may have no analogue in current climates or those of the recent geological past. Experimental field manipulations and laboratory studies indicate that plants will exhibit complex responses in photosynthesis, growth rates, phenology and reproductive functioning due to this combination of increasing temperatures, changing seasonality and increasing levels of CO(2). The resulting changes in the abundance, distribution, growth rates and production of fruit and phenology of plant species will in turn impact animal populations. In predicting what the future biota of the 'New Arctic' will be like and developing appropriate conservation strategies, Grinnellian niche-based approaches are likely to be insufficient, and experimental ecological studies of organism response to specific anticipated changes in climate are crucial.

Electromechanical coupling between skeletal and cardiac muscle. Implications for infarct repair.

Skeletal myoblasts form grafts of mature muscle in injured hearts, and these grafts contract when exogenously stimulated. It is not known, however, whether cardiac muscle can form electromechanical junctions with skeletal muscle and induce its synchronous contraction. Here, we report that undifferentiated rat skeletal myoblasts expressed N-cadherin and connexin43, major adhesion and gap junction proteins of the intercalated disk, yet both proteins were markedly downregulated after differentiation into myo-tubes. Similarly, differentiated skeletal muscle grafts in injured hearts had no detectable N-cadherin or connexin43; hence, electromechanical coupling did not occur after in vivo grafting. In contrast, when neonatal or adult cardiomyocytes were cocultured with skeletal muscle, approximately 10% of the skeletal myotubes contracted in synchrony with adjacent cardiomyocytes. Isoproterenol increased myotube contraction rates by 25% in coculture without affecting myotubes in monoculture, indicating the cardiomyocytes were the pacemakers. The gap junction inhibitor heptanol aborted myotube contractions but left spontaneous contractions of individual cardiomyocytes intact, suggesting myotubes were activated via gap junctions. Confocal microscopy revealed the expression of cadherin and connexin43 at junctions between myotubes and neonatal or adult cardiomyocytes in vitro. After microinjection, myotubes transferred dye to neonatal cardiomyocytes via gap junctions. Calcium imaging revealed synchronous calcium transients in cardiomyocytes and myotubes. Thus, cardiomyocytes can form electromechanical junctions with some skeletal myotubes in coculture and induce their synchronous contraction via gap junctions. Although the mechanism remains to be determined, if similar junctions could be induced in vivo, they might be sufficient to make skeletal muscle grafts beat synchronously with host myocardium.

Implications for Geophysics of the Precise Measurement of the Earth's Rotation.

A radio interferometer could yield an error on the order of 10(-9) second at the semidiurnal frequency. With errors of this magnitude, yearly changes in the rate at which the earth's rotation is slowing down could be determined. The proposed interferometer could also yield significant improvements in the determination of the Love number k and its variation with frequency, and in the changes in angular momentum of the atmosphere for periods greater than 1 week.

Reserpine: effect on structure of heart muscle.

We examined the ultrastructure of hearts from dogs given reserpine intramuscularly for 4 days, and from untreated dogs. Sections of the myocardium from treated dogs invariably revealed mitochondrial abnormalities at the 5th and 14th days. These included fragmentation and loss of structure of the cristae, and cyst formation. The appearance at 25 days in the treated as well as in all the untreated dogs was normal. We concluded that reserpine in the dose used produces marked structural changes in the mitochondria of heart muscle, and that these changes are reversible. These changes may account for the myocardial depression sometimes seen after administration of reserpine.

Laser ranging retro-reflector: continuing measurements and expected results.

After successful acquisition in August of reflected ruby laser pulses from the Apollo 11 laser ranging retro-reflector (LRRR) with the telescopes at the Lick and McDonald observatories, repeated measurements of the round-trip travel time of light have been made from the McDonald Observatory in September with an equivalent range precision of +/-2.5 meters. These acquisition period observations demonstrated the performance of the LRRR through lunar night and during sunlit conditions on the moon. Instrumentation activated at the McDonald Observatory in October has yielded a precision of +/-0.3 meter, and improvement to +/-0.15 meter is expected shortly. Continued monitoring of the changes in the earth-moon distance as measured by the round-trip travel time of light from suitably distributed earth stations is expected to contribute to our knowledge of the earth-moon system.

A phase I clinical study of intratumorally administered VB4-845, an anti-epithelial cell adhesion molecule recombinant fusion protein, in patients with squamous cell carcinoma of the head and neck.

VB4-845 is a novel recombinant fusion protein that targets the epithelial cellular adhesion molecule (EpCAM). This initial clinical trial was conducted to determine the maximum tolerated dose of intratumoral injections in patients with advanced squamous cell carcinoma of the head and neck and to assess pharmacokinetics and immunogenicity. Twenty-four patients with advanced, recurrent squamous cell carcinoma of the head and neck received two cycles of five daily intratumoral VB4-845 injections of 20, 40, 80, 130, 200, or 280 microg. The maximum tolerated dose was established to be 280 microg administered daily for 5 days. Common adverse events were pain due to intratumoral injection and reversibly elevated liver enzymes. Of the 24 patients, 15 had detectable blood levels with a mean drug half-life of 4.0 +/- 0.3 h. VB4-845 reduced or stabilized tumors in 71.4% of epithelial cell adhesion molecule-positive patients. VB4-845 intratumoral injection therapy was well tolerated and feasible.

Leptin and the risk of Barrett's oesophagus.

BACKGROUND: Obesity is associated with increased risks of Barrett's oesophagus and oesophageal adenocarcinoma. Alterations in serum leptin and adiponectin, obesity-related cytokines, have been linked with several cancers and have been postulated as potential mediators of obesity-related carcinogenesis; however, the relationship with Barrett's oesophagus remains unexplored. METHODS: Serum leptin and adiponectin concentrations were measured on two subsets of participants within a case-control study conducted in Brisbane, Australia. Cases were people aged 18-79 years with histologically confirmed Barrett's oesophagus newly diagnosed between 2003 and 2006. Population controls, frequency matched by age and sex to cases, were randomly selected from the electoral roll. Phenotype and medical history data were collected through structured, self-completed questionnaires. Odds ratios (OR) and 95% CI were calculated using multivariable logistic regression analysis. RESULTS: In the pilot analysis (51 cases, 67 controls) risks of Barrett's oesophagus were highest among those in the highest quartile of serum leptin (OR 4.6, 95% CI 0.6 to 33.4). No association was seen with adiponectin. In the leptin validation study (306 cases, 309 controls), there was a significant threefold increased risk of Barrett's oesophagus among men in the highest quartile of serum leptin (OR 3.3, 95% CI 1.7 to 6.6) and this persisted after further adjustment for symptoms of gastro-oesophageal reflux (OR 2.4, 95% CI 1.1 to 5.2). In contrast, the risk of Barrett's oesophagus among women decreased with increasing serum leptin concentrations. CONCLUSIONS: High serum leptin is associated with an increased risk of Barrett's oesophagus among men but not women. This association is not explained simply by higher body mass or gastro-oesophageal reflux among cases. The mechanism remains to be determined.

Human GAP-43: its deduced amino acid sequence and chromosomal localization in mouse and human.

The growth-associated protein (GAP-43) is considered a crucial component of an effective regenerative response in the nervous system. Its phosphorylation by protein kinase C correlates with long-term potentiation. Sequence analysis of human cDNAs coding for this protein shows that the human GAP-43 gene is highly homologous to the rat gene; this homology extends into the 3'-untranslated region. However, the human protein contains a 10 amino acid insert. Somatic cell hybrids demonstrate localization of the GAP-43 gene to human chromosome 3 and to mouse chromosome 16.

Treatment foster care for improving outcomes in children and young people.

BACKGROUND: Treatment foster care (TFC) is a foster family-based intervention that aims to provide young people (and, where appropriate, their families) with a tailored programme designed to effect positive changes in their lives. TFC was designed specifically to cater for the needs of children whose difficulties or circumstances place them at risk of multiple placements and/or more restrictive placements such as hospital or secure residential or youth justice settings. OBJECTIVES: To assess the impact of TFC on psychosocial and behavioural outcomes, delinquency, placement stability, and discharge status for children and adolescents who require out-of-home placement. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register (CENTRAL) 2006 (Issue 4), MEDLINE (1966 to January 2007), CINAHL (1982 to December 2006), PsycINFO (1872 to January 2007), ASSIA (1987 to January 2007), LILACS (1982 to January 2007), ERIC (1966 to January 2007), Sociological Abstracts (1963 to January 2007), and the National Research Register 2006 (Issue 4). SELECTION CRITERIA: Included studies were randomised controlled trials investigating the effectiveness of TFC with children and young people up to the age of 18 who, for reasons of severe medical, social, psychological and behavioural problems, were placed in out of home care in restrictive settings (e.g. secure residential care, psychiatric hospital) or at risk of placement in such settings. DATA COLLECTION AND ANALYSIS: Titles and abstracts identified in the search were independently assessed for eligibility by the two authors (GM and WT) who also extracted and entered into REVMAN. Date were synthesised on the few occasions where this was possible. Results are presented in tabular, graphical (forest plots) and textual form. MAIN RESULTS: Five studies including 390 participants were included in this review. Data suggest that treatment foster care may be a useful intervention for children and young people with complex emotional, psychological and behavioural need, who are at risk of placements in non-family settings that restrict their liberty and opportunities for social inclusion. AUTHORS' CONCLUSIONS: Although the inclusion criteria for this systematic review set a study design threshold higher than that of previous reviews, the results mirror those of earlier reviews but also highlights the tendency of the perceived effectiveness of popular interventions to outstrip their evidence base. Whilst the results of individual studies generally indicate that TFC is a promising intervention for children and youth experiencing mental health problems, behavioural problems or problems of delinquency, the evidence base is less robust than that usually reported.

WITHDRAWN: Home-based support for disadvantaged adult mothers.

BACKGROUND: Babies born to socio-economically disadvantaged mothers are at higher risk of a range of problems in infancy. Home visiting programs are thought to improve outcomes, both for mothers and children, largely through advice and support. OBJECTIVES: To assess the effectiveness of home visiting programmes for women who have recently given birth and who are socially or economically disadvantaged. SEARCH STRATEGY: We searched the following electronic databases: The Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 3, 2006); MEDLINE (1966 to March 2006); EMBASE (1980 to 2006 week 12); CINAHL (1982 to March week 4 2006); PsycINFO (1872 to March week 4 2006); ASSIA (1987 to March 2006); LILACS (1982 to March 2006); and Sociological Abstracts(1963 to March 2006). We searched grey literature using ZETOC (1993 to March 2006); Dissertation Abstracts International (late 1960s to 2006); and SIGLE (1980 to March 2006). We also undertook communication with published authors about ongoing or unpublished research. SELECTION CRITERIA: Included studies were randomised controlled trials investigating the efficacy of home visiting directed at disadvantaged adult mothers. DATA COLLECTION AND ANALYSIS: Two reviewers (EC and JP or CB) independently assessed titles and abstracts identified in the search for eligibility. Data were extracted and entered into RevMan (EC, JP and CB), synthesised and presented in both written and graphical form (forest plots). Outcomes included in this review were established at the protocol stage by an international steering group. The review does not report on all outcomes reported in included studies. MAIN RESULTS: We included 11 studies with 4751 participants in this review. Data show no statistically significant differences for those receiving home visiting, either for maternal outcomes (maternal depression, anxiety, the stress associated with parenting, parenting skills, child abuse risk or potential or breastfeeding) or child outcomes (preventive health care visits, psychosocial health, language development, behaviour problems or accidental injuries. Evidence about uptake of immunisations is mixed, and the data on child maltreatment difficult to interpret. AUTHORS' CONCLUSIONS: This review suggests that for disadvantaged adult women and their children, there is currently no evidence to support the adoption of home visiting as a means of improving maternal psychosocial health, parenting or outcomes for children. For reasons discussed in the review, this does not amount to a conclusion that home visiting programmes are ineffective, but indicates a need to think carefully about the problems that home visiting might influence, and improvements in the conduct of outcome studies in this area.

WITHDRAWN: Home-based support for disadvantaged teenage mothers.

BACKGROUND: Babies born to socio-economically disadvantaged mothers are at higher risk of injury, abuse or neglect and health problems than babies born to more affluent mothers; disadvantaged teenage mothers are at particular risk of adverse outcomes. Home-visiting programs are thought to improve outcomes for both mothers and children, largely through advice and support. OBJECTIVES: To assess the effectiveness of home-visiting programmes for women who have recently given birth and who are socially or economically disadvantaged. SEARCH STRATEGY: The following electronic databases were searched: CENTRAL (2006, Issue 3); MEDLINE (1966 to March 2006); EMBASE (1980 to week 12 2006); CINAHL (1982 to March week 4 2006); PsycINFO (1872 to March week 4 2006); ASSIA (1987 to March 2006); LILACS (1982 to March 2006); and Sociological Abstracts (1963 to March 2006). Grey literature was also be searched using ZETOC (1993 to March 2006); Dissertation Abstracts International (late 1960s to 2006); and SIGLE (1980 to March 2006). Communication with published authors about ongoing or unpublished research was also undertaken. SELECTION CRITERIA: Included studies were randomised controlled trials investigating the efficacy of home visiting directed at teenage mothers. DATA COLLECTION AND ANALYSIS: Titles and abstracts identified in the search were independently assessed for eligibility by two review authors (EC and JP or CB). Data were extracted and entered into RevMan (EC, JP and CB), synthesised and presented in both written and graphical form (forest plots). Outcomes included in this review were established at the protocol stage by an international steering group. The review did not report on all outcomes reported in included studies. MAIN RESULTS: Five studies with 1838 participants were included in this review. Data from single studies provided support for the effectiveness of home visiting on some outcomes, but the evidence overall provided only limited support for the effectiveness of home visiting as a means of improving the range of maternal and child outcomes considered in this review. AUTHORS' CONCLUSIONS: This review suggests there is only limited evidence that home-visiting programmes of the kind described in this review can impact positively on the quality of parenting of teenage mothers or on child development outcomes for their offspring. For reasons discussed in the review, this does not amount to a conclusion that home-visiting programmes are ineffective but indicates a need to think carefully about the problems that home visiting might influence and about improvements in the conduct and reporting of outcome studies in this area.

The effects of helium-hyperoxia on 6-min walking distance in COPD: a randomized, controlled trial.

BACKGROUND: We hypothesized that breathing helium-hyperoxia (HeO2) would significantly improve 6-min walking test (6MWT) distance in COPD subjects. METHODS: This was a blinded, randomized crossover study. At visit 1, we assessed pulmonary function, exercise capacity, and 6MWT distance. Visits 2 and 3 consisted of four 6MWTs in which the following different inspired gases were used: room air (RA) by mask; 100% O2 by mask (mask O2); 100% O2 by nasal prongs (nasal O2); and 70% He/30% O2 by mask (HeO2). Walking distance, shortness of breath, leg fatigue, O2 saturation, and heart rate (HR) were assessed. RESULTS: Sixteen COPD subjects participated (mean FEV(1)/FVC ratio [+/- SD], 48 +/- 8%; mean FEV1, 55 +/- 13% predicted). Subjects walked farther when breathing HeO2 (564 m) compared to RA (497 m; p < 0.001), mask O2 (520 m; p < 0.001), or nasal O2 (528 m; p < 0.001). Despite the increased distance walked while breathing HeO2, there was no increase in shortness of breath or leg fatigue. There was desaturation when breathing RA (8%; p < 0.001) and nasal O2 (5%; p < 0.001), which was reduced when breathing HeO2 (3%; difference not significant) and mask O(2) (0%; difference not significant). There were no significant differences in HR in the four 6MWTs. CONCLUSIONS: The use of HeO2 increased 6MWT distance in COPD subjects more than either mask O2 or nasal O2 compared to RA. The increased walking distance was not associated with increased shortness of breath or leg fatigue. The results suggest that clinical benefit would be obtained by administering HeO2 during exercise, which may have significant clinical implications for the management of COPD patients.

Cognitive-behavioural training interventions for assisting foster carers in the management of difficult behaviour.

BACKGROUND: The provision of training for foster carers is now seen as an important factor contributing to the successful outcome of foster care placements. Since the late 1960s, foster carer training programs have proliferated, and few of the many published and unpublished training curricula have been systematically assessed and evaluated. The advent of cognitive-behavioural therapy (CBT) and the research evidence demonstrating its effectiveness as a psychotherapeutic treatment of choice, has prompted many working in the social care field to devise CBT-based training programmes. CBT approaches to foster care training derive from a 'skill-based' training format that also seeks to identify and correct problematic thinking patterns that are associated with dysfunctional behaviour by changing and/or challenging maladaptive thoughts and beliefs. OBJECTIVES: To assess the effectiveness of cognitive-behavioural training interventions in improving a) looked-after children's behavioural/relationship problems, b) foster carers' psychological well-being and functioning, c) foster family functioning, d) foster agency outcomes. SEARCH STRATEGY: We searched databases including: CENTRAL (Cochrane Library Issue 3, 2006), MEDLINE (January 1966 to September 2006), EMBASE (January 1980 to April 2004), CINAHL (January 1982 to April 2004), PsycINFO (January 1872 to April 2004), ASSIA (January 1987 to April 2004), LILACS (up to April 2004), ERIC (January 1965 to April 2004), Sociological Abstracts (January 1963 to April 2004), and the National Research Register 2004 (Issue 3). We contacted experts in the field concerning current research. SELECTION CRITERIA: All studies in which participants were foster parents/carers, and who were allocated by random or quasi-random methods to a CBT-based training intervention (in a group and/or one-to-one settings) versus a no-treatment or wait-list control, were selected. DATA COLLECTION AND ANALYSIS: Data from the six eligible trials (total n = 463 ) were extracted and entered into RevMan. Results were synthesised and presented in both graphical (forest plots) and narrative form (where insufficient data were provided for effect size computations). MAIN RESULTS: Training interventions evaluated to date appear to have very little effect on outcomes relating to looked-after children, assessed in relation to psychological functioning, extent of behavioural problems and interpersonal functioning. Results relating to foster carer(s) outcomes also show no evidence of effectiveness in measures of behavioural management skills, attitudes and psychological functioning. Analysis pertaining to fostering agency outcomes did not show any significant results. AUTHORS' CONCLUSIONS: There is currently little evidence about the efficacy of CBT-based training intervention for foster carers. The need for further research in this area is highlighted.