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PDF file - 636KB, Supplemental Table S1: information of the GBM lines used in this paper. Supplemental Table S2: information of the patient clinical data for Figure 1. Supplemental Table S3: Percentage of cells positive for staining with PRMT5 in spontaneous high grade astrocytoma from Mut3 strain (GFAP-cre; cisNf1-/+; P53-/-) and normal brain tissue from wild-type control mouse stained by PRMT5 and ki-67 antibody. Supplemental table S4. GBM cell line (U251) was transfected by scramble control or si-PRMT5. Affymetrix microarray genechip was performed in three independent experiments to evaluate genes up-regulated with PRMT5 silencing.

PDF file - 1690KB, Supplemental Figure S1. PRMT5 is over-expressed in human GBM cell lines. Supplemental Figure S2: High grade astrocytomas Supplemental Figure S3: efficacy and specificity of PRMT5 knock-down by lead siRNA. Supplemental Figure S4: PRMT5 Knockdown promotes cell death of human GBM cells Supplemental Figure S5: si-PRMT5 induced cell death is P53-independent Supplemental Figure S6: Decreased ST7 expression correlates with worse survival in all glioma patients (grade I-IV). Supplemental Figure S7: Over-expression of ST7 in three GBM cell lines was confirmed by real-time PCR and western blot (top panels).

Glioblastoma is the most common and aggressive histologic subtype of brain cancer with poor outcomes and limited treatment options. Here, we report the selective overexpression of the protein arginine methyltransferase PRMT5 as a novel candidate theranostic target in this disease. PRMT5 silences the transcription of regulatory genes by catalyzing symmetric dimethylation of arginine residues on histone tails. PRMT5 overexpression in patient-derived primary tumors and cell lines correlated with cell line growth rate and inversely with overall patient survival. Genetic attenuation of PRMT5 led to cell-cycle arrest, apoptosis, and loss of cell migratory activity. Cell death was p53-independent but caspase-dependent and enhanced with temozolomide, a chemotherapeutic agent used as a present standard of care. Global gene profiling and chromatin immunoprecipitation identified the tumor suppressor ST7 as a key gene silenced by PRMT5. Diminished ST7 expression was associated with reduced patient survival. PRMT5 attenuation limited PRMT5 recruitment to the ST7 promoter, led to restored expression of ST7 and cell growth inhibition. Finally, PRMT5 attenuation enhanced glioblastoma cell survival in a mouse xenograft model of aggressive glioblastoma. Together, our findings defined PRMT5 as a candidate prognostic factor and therapeutic target in glioblastoma, offering a preclinical justification for targeting PRMT5-driven oncogenic pathways in this deadly disease. Cancer Res; 74(6); 1752–65. ©2014 AACR.

Cognitive behavioural therapy is an effective treatment for anxiety disorders in children and young people; however, many do not benefit. Behavioural exposure appears to be the critical ingredient in the treatment of anxiety disorders. Research with adults has identified innovative strategies to optimise exposure-based treatments, yet it is not clear how to optimise the effects of exposure for children and young people. This review was a preliminary exploration of the association between potential optimisation strategies and treatment procedures and outcomes for the treatment of child anxiety symptoms/disorders. We searched Psych-Info and Medline databases using a systematic search strategy and identified 29 articles. We found preliminary evidence that some specific strategies may enhance the effects of exposure, such as dropping safety behaviours, parents and therapists discouraging avoidance, and the use of homework. However, not one significant finding was replicated by another study for the same timepoint using the same methodology. To a large degree, this lack of replication reflects a limited number of studies combined with a lack of consistency across studies around conceptualisations, methodological approaches, and outcome measures making it difficult to make meaningful comparisons between studies and draw firm conclusions. Examination is needed of a wide range of theoretically-driven potential optimisation strategies using methodologically robust, preclinical studies with children and young people. Furthermore, the methods used in future research must enable comparisons across studies and explore developmental differences in the effects of particular optimisation strategies.

BACKGROUND Distressing cancer pain remains a serious symptom management issue for patients and family caregivers, especially in the home setting. Technology can support home-based cancer symptom management but must consider the experience of both patients and family caregivers, as well as the broader environmental context. OBJECTIVE To test feasibility and acceptability of a smart health sensing system, Behavioral and Environmental Sensing and Intervention for Cancer (BESI-C), designed to monitor, and ultimately support management of, cancer pain in the home setting. METHODS Dyads of patients with cancer and their primary family caregivers were recruited from an outpatient palliative care clinic at an academic medical center in the Southeastern U.S. BESI-C was deployed in dyad homes for approximately two weeks each. Data were collected via: 1) environmental sensors that measure ambient noise, humidity, barometric pressure, light, and temperature; 2) Bluetooth beacons to help localize dyad position; and 3) smart watches worn by both patients and caregivers equipped with heartrate monitors, accelerometers, and a custom application to deliver ecological momentary assessments (EMAs). EMAs enabled dyads to record and characterize pain events from both their own and their partner’s perspective. Sensor data streams were integrated to describe and explore the context for cancer pain events. Feasibility was assessed technically (by scoring each deployment regarding fidelity of data capture across system components) and procedurally (e.g., deployment process, participant recruitment). Acceptability was assessed by post-deployment surveys and structured interviews with participants. RESULTS 5 deployments (n=10 participants; 5 dyads of patients and primary family caregivers) were completed, and a total of 283 unique pain events were recorded. Using our ‘BESI-C Performance Scoring Instrument’, the overall feasibility technical score for deployments was 86.4/100. Procedural feasibility challenges included: rural location of dyads; smart watch battery life and EMA reliability; and length of time required for deployment installation. Post-deployment acceptability Likert surveys (1, strongly disagree; 5, strongly agree), found dyads disagreed that BESI-C was a burden (1.7/5) or compromised their privacy (1.9/5) and agreed the system collected helpful information to better manage cancer pain (4.6/5). Participants also expressed interest in seeing their own individual data (4.4/5) and strongly agreed it is important that data collected by BESI-C are shared with their respective partner (4.8/5) and healthcare provider (4.8/5). Qualitative feedback from participants suggests BESI-C positively improved communication regarding pain management. Importantly, we demonstrated proof of concept that seriously ill patients and their caregivers will mark pain events in real time using a smart watch. CONCLUSIONS It is feasible to deploy BESI-C, and dyads find the system acceptable. Leveraging human-centered design and the collection of heterogenous environmental, physiological, and behavioral data, BESI-C offers an innovative approach to monitor cancer pain, mitigate escalation of pain and distress, and improve symptom management self-efficacy. Future work will: (shorter-term) 1) test BESI-C in a larger, more diverse sample; 2) continue to streamline system architecture; 3) deploy a no-contact, self-installation system in response to the COVID-19 pandemic and to enhance scalability; 4) explore how to best share data visualizations of collected data with key stakeholders; and 5) (longer-term) inform design of and deliver just-in-time personalized pain management interventions to patients and caregivers. CLINICALTRIAL n/a INTERNATIONAL REGISTERED REPORT RR2-10.2196/16178

Publisher's version (útgefin grein), Background Childhood Social Anxiety Disorder (SAD) is common and impairing. The recommended treatment is a disorder specific form of cognitive behavioural therapy (CBT) that includes social skills training and, whilst they appear to be more effective than more general treatments, it is not clear whether social skills training is the critical component involved in improved outcomes, particularly given that evidence for the relationship between social anxiety and social skills deficits in children is inconsistent. This may be partly due to an overlap in their observable features, and because the nature of the association may vary in different contexts (e.g. according to child age). An alternative approach is to examine the association between social anxiety and the social cognitive capacities that underpin social skills. This paper aims to examine the association between social anxiety and social cognition in children and adolescents, and examine conceptual and methodological moderators of this relationship. Methods Papers published between 1980 and 2019 were screened systematically. Fifty studies were identified from which an effect size could be calculated for the relationship between social anxiety and social cognition, including 15,411 children and adolescents. Results An overall significant, but moderate effect (r = -.15) was identified, where increased social anxiety was associated with lower social cognitive ability. Moderation analyses revealed specific associations within studies examining social anxiety among participants with and without ASD who were older than 7 years old, and studies assessing the relationship between social anxiety and specific aspects of Theory of Mind (ToM). No significant association was identified between social anxiety and emotion recognition. Conclusions Significant associations between social anxiety and social cognitive abilities appear to be accounted for by elevated social anxiety among children with ASD, and those with difficulties in specific aspects of ToM but not broader social skills, such as emotion recognition. This reinforces the importance of accurately identifying and treating social anxiety within ASD populations. In addition, treatments for social anxiety among neurotypical populations may benefit from targeting particular aspects of ToM rather than emotion recognition and other broad social skills., National Institute for Health Research (NIHR) Grant Number: NIHR-RP-2014-04-018 University of Reading, "Peer Reviewed"

BACKGROUND Inadequately managed pain is a serious problem for patients with cancer and those who care for them. Smart health systems can help with remote symptom monitoring and management, but they must be designed with meaningful end-user input. OBJECTIVE This study aims to understand the experience of managing cancer pain at home from the perspective of both patients and family caregivers to inform design of the Behavioral and Environmental Sensing and Intervention for Cancer (BESI-C) smart health system. METHODS This was a descriptive pilot study using a multimethod approach. Dyads of patients with cancer and difficult pain and their primary family caregivers were recruited from an outpatient oncology clinic. The participant interviews consisted of (1) open-ended questions to explore the overall experience of cancer pain at home, (2) ranking of variables on a Likert-type scale (0, no impact; 5, most impact) that may influence cancer pain at home, and (3) feedback regarding BESI-C system prototypes. Qualitative data were analyzed using a descriptive approach to identity patterns and key themes. Quantitative data were analyzed using SPSS; basic descriptive statistics and independent sample t tests were run. RESULTS Our sample (n=22; 10 patient-caregiver dyads and 2 patients) uniformly described the experience of managing cancer pain at home as stressful and difficult. Key themes included (1) unpredictability of pain episodes; (2) impact of pain on daily life, especially the negative impact on sleep, activity, and social interactions; and (3) concerns regarding medications. Overall, taking pain medication was rated as the category with the highest impact on a patient’s pain (=4.79), followed by the categories of wellness (=3.60; sleep quality and quantity, physical activity, mood and oral intake) and interaction (=2.69; busyness of home, social or interpersonal interactions, physical closeness or proximity to others, and emotional closeness and connection to others). The category related to environmental factors (temperature, humidity, noise, and light) was rated with the lowest overall impact (=2.51). Patients and family caregivers expressed receptivity to the concept of BESI-C and reported a preference for using a wearable sensor (smart watch) to capture data related to the abrupt onset of difficult cancer pain. CONCLUSIONS Smart health systems to support cancer pain management should (1) account for the experience of both the patient and the caregiver, (2) prioritize passive monitoring of physiological and environmental variables to reduce burden, and (3) include functionality that can monitor and track medication intake and efficacy; wellness variables, such as sleep quality and quantity, physical activity, mood, and oral intake; and levels of social interaction and engagement. Systems must consider privacy and data sharing concerns and incorporate feasible strategies to capture and characterize rapid-onset symptoms.

Computational representations of the semantic knowledge embedded within clinical practice guidelines (CPGs) may be a significant aid in creating computer interpretable guidelines (CIGs). Formalizing plain text CPGs into CIGs manually is a laborious and burdensome task, even using CIG tools and languages designed to improve the process. Natural language understanding (NLU) systems perform automated reading comprehension, parsing text and using reasoning to convert syntactic information from unstructured text into semantic information. Influenced by successful systems used in other domains, we present the architecture for a system which uses NLU approaches to create semantic representations of entire CPGs. In the future, these representations may be used to generate CIGs.

Background An estimated 60%-90% of patients with cancer experience moderate to severe pain. Poorly managed cancer pain negatively affects the quality of life for both patients and their family caregivers and can be a particularly challenging symptom to manage at home. Mobile and wireless technology (“Smart Health”) has significant potential to support patients with cancer and their family caregivers and empower them to safely and effectively manage cancer pain. Objective This study will deploy a package of sensing technologies, known as Behavioral and Environmental Sensing and Intervention for Cancer (BESI-C), and evaluate its feasibility and acceptability among patients with cancer-family caregiver dyads. Our primary aims are to explore the ability of BESI-C to reliably measure and describe variables relevant to cancer pain in the home setting and to better understand the dyadic effect of pain between patients and family caregivers. A secondary objective is to explore how to best share collected data among key stakeholders (patients, caregivers, and health care providers). Methods This descriptive two-year pilot study will include dyads of patients with advanced cancer and their primary family caregivers recruited from an academic medical center outpatient palliative care clinic. Physiological (eg, heart rate, activity) and room-level environmental variables (ambient temperature, humidity, barometric pressure, light, and noise) will be continuously monitored and collected. Behavioral and experiential variables will be actively collected when the caregiver or patient interacts with the custom BESI-C app on their respective smart watch to mark and describe pain events and answer brief, daily ecological momentary assessment surveys. Preliminary analysis will explore the ability of the sensing modalities to infer and detect pain events. Feasibility will be assessed by logistic barriers related to in-home deployment, technical failures related to data capture and fidelity, smart watch wearability issues, and patient recruitment and attrition rates. Acceptability will be measured by dyad perceptions and receptivity to BESI-C through a brief, structured interview and surveys conducted at deployment completion. We will also review summaries of dyad data with participants and health care providers to seek their input regarding data display and content. Results Recruitment began in July 2019 and is in progress. We anticipate the preliminary results to be available by summer 2021. Conclusions BESI-C has significant potential to monitor and predict pain while concurrently enhancing communication, self-efficacy, safety, and quality of life for patients and family caregivers coping with serious illness such as cancer. This exploratory research offers a novel approach to deliver personalized symptom management strategies, improve patient and caregiver outcomes, and reduce disparities in access to pain management and palliative care services. International Registered Report Identifier (IRRID) DERR1-10.2196/16178

BACKGROUND An estimated 60%-90% of patients with cancer experience moderate to severe pain. Poorly managed cancer pain negatively affects the quality of life for both patients and their family caregivers and can be a particularly challenging symptom to manage at home. Mobile and wireless technology (“Smart Health”) has significant potential to support patients with cancer and their family caregivers and empower them to safely and effectively manage cancer pain. OBJECTIVE This study will deploy a package of sensing technologies, known as Behavioral and Environmental Sensing and Intervention for Cancer (BESI-C), and evaluate its feasibility and acceptability among patients with cancer-family caregiver dyads. Our primary aims are to explore the ability of BESI-C to reliably measure and describe variables relevant to cancer pain in the home setting and to better understand the dyadic effect of pain between patients and family caregivers. A secondary objective is to explore how to best share collected data among key stakeholders (patients, caregivers, and health care providers). METHODS This descriptive two-year pilot study will include dyads of patients with advanced cancer and their primary family caregivers recruited from an academic medical center outpatient palliative care clinic. Physiological (eg, heart rate, activity) and room-level environmental variables (ambient temperature, humidity, barometric pressure, light, and noise) will be continuously monitored and collected. Behavioral and experiential variables will be actively collected when the caregiver or patient interacts with the custom BESI-C app on their respective smart watch to mark and describe pain events and answer brief, daily ecological momentary assessment surveys. Preliminary analysis will explore the ability of the sensing modalities to infer and detect pain events. Feasibility will be assessed by logistic barriers related to in-home deployment, technical failures related to data capture and fidelity, smart watch wearability issues, and patient recruitment and attrition rates. Acceptability will be measured by dyad perceptions and receptivity to BESI-C through a brief, structured interview and surveys conducted at deployment completion. We will also review summaries of dyad data with participants and health care providers to seek their input regarding data display and content. RESULTS Recruitment began in July 2019 and is in progress. We anticipate the preliminary results to be available by summer 2021. CONCLUSIONS BESI-C has significant potential to monitor and predict pain while concurrently enhancing communication, self-efficacy, safety, and quality of life for patients and family caregivers coping with serious illness such as cancer. This exploratory research offers a novel approach to deliver personalized symptom management strategies, improve patient and caregiver outcomes, and reduce disparities in access to pain management and palliative care services. INTERNATIONAL REGISTERED REPORT DERR1-10.2196/16178

Background Inadequately managed pain is a serious problem for patients with cancer and those who care for them. Smart health systems can help with remote symptom monitoring and management, but they must be designed with meaningful end-user input. Objective This study aims to understand the experience of managing cancer pain at home from the perspective of both patients and family caregivers to inform design of the Behavioral and Environmental Sensing and Intervention for Cancer (BESI-C) smart health system. Methods This was a descriptive pilot study using a multimethod approach. Dyads of patients with cancer and difficult pain and their primary family caregivers were recruited from an outpatient oncology clinic. The participant interviews consisted of (1) open-ended questions to explore the overall experience of cancer pain at home, (2) ranking of variables on a Likert-type scale (0, no impact; 5, most impact) that may influence cancer pain at home, and (3) feedback regarding BESI-C system prototypes. Qualitative data were analyzed using a descriptive approach to identity patterns and key themes. Quantitative data were analyzed using SPSS; basic descriptive statistics and independent sample t tests were run. Results Our sample (n=22; 10 patient-caregiver dyads and 2 patients) uniformly described the experience of managing cancer pain at home as stressful and difficult. Key themes included (1) unpredictability of pain episodes; (2) impact of pain on daily life, especially the negative impact on sleep, activity, and social interactions; and (3) concerns regarding medications. Overall, taking pain medication was rated as the category with the highest impact on a patient’s pain (=4.79), followed by the categories of wellness (=3.60; sleep quality and quantity, physical activity, mood and oral intake) and interaction (=2.69; busyness of home, social or interpersonal interactions, physical closeness or proximity to others, and emotional closeness and connection to others). The category related to environmental factors (temperature, humidity, noise, and light) was rated with the lowest overall impact (=2.51). Patients and family caregivers expressed receptivity to the concept of BESI-C and reported a preference for using a wearable sensor (smart watch) to capture data related to the abrupt onset of difficult cancer pain. Conclusions Smart health systems to support cancer pain management should (1) account for the experience of both the patient and the caregiver, (2) prioritize passive monitoring of physiological and environmental variables to reduce burden, and (3) include functionality that can monitor and track medication intake and efficacy; wellness variables, such as sleep quality and quantity, physical activity, mood, and oral intake; and levels of social interaction and engagement. Systems must consider privacy and data sharing concerns and incorporate feasible strategies to capture and characterize rapid-onset symptoms.

To assess postsurgical clinical and economic outcomes of patients who received local infiltration containing liposomal bupivacaine versus traditional bupivacaine for pain management following total hip arthroplasty (THA).This retrospective study included two groups of consecutive patients undergoing THA. The experimental group received local infiltration with a combination of liposomal bupivacaine, bupivacaine HCl 0.25% with epinephrine 1:200,000, and ketorolac for postsurgical analgesia. The historical control group received the previous standard of care: local infiltration with a combination of bupivacaine HCl 0.25% with epinephrine 1:200,000 and ketorolac. Key outcomes included distance walked, length of stay (LOS), opioid medication use, numeric pain scores, hospital charges, hospital costs, all-cause 30 day readmission rate, and adverse events (AEs). Both unadjusted and adjusted (i.e. age, sex, insurance type, living situation, body mass index, procedure side, and comorbidity) outcomes were compared between the two groups.The experimental group (n = 64) demonstrated statistically significant improvement versus the historical control group (n = 66) in mean distance walked on discharge day (249.2 vs. 180.0 feet; unadjusted p = .025, adjusted p = .070), mean LOS (2.0 vs. 2.7 days; p .001, p = .002), proportion of patients who used opioid rescue medication on postoperative day (POD) 1 (29.7% vs. 56.1%; p = .002, p = .003) and POD 2 (7.8% vs. 30.3%; p = .001, p = .003), mean cumulative area under the curve for pain score on POD 0 (127.6 vs. 292.5; p .001, both), POD 1 (92.9 vs. 185.0; p .001, both), and POD 2 (93.8 vs. 213.8; p = .006, both). Among a subgroup of patients with available financial information, mean hospital charges were lower in the experimental group ($43,794 [n = 24] vs. $48,010 [n = 66]; p .001, both). Rates of all-cause 30 day readmission and AEs were not significantly different between groups. No falls occurred.Infiltration at the surgical site with liposomal bupivacaine was associated with improved postsurgical outcomes when compared with traditional bupivacaine in patients undergoing THA.

This report presents an unusual case of ST elevation on induction of anaesthesia in a patient undergoing an elective, noncardiac surgical procedure. Through scrutiny of this case and its unanticipated events, together with the subsequent workup and management, the diagnosis of coronary artery vasospasm may be appreciated as an important entity of coronary artery disease. It serves to highlight coronary artery vasospasm as an underappreciated diagnosis, to allow the anaesthetist to anticipate it as a potential risk in certain populations, and to distinguish it from other coronary artery disease and to institute appropriate management.Keywords: coronary, artery, vasospasm, myocardial infarction, intraoperativeSouth Afr J Anaesth Analg 2013;19(5):270-273

Background Psychoeducation is an essential component of postdiagnostic care for people with ASD (autism spectrum disorder), but there is currently no evidence base for clinical practice. We designed, manualised and evaluated PEGASUS (psychoeducation group for autism spectrum understanding and support), a group psychoeducational programme aiming to enhance the self-awareness of young people with ASD by teaching them about their diagnosis. Methods This single-blind RCT (randomised control trial) involved 48 young people (9–14 years) with high-functioning ASD. Half were randomly assigned to PEGASUS, administered in six weekly group sessions, with the others receiving no additional intervention. ASD-related self-awareness, the primary outcome, was evaluated using the bespoke Autism Knowledge Quiz (AKQ). Secondary outcome measures included the Rosenberg Self-Esteem Scale. All measures were collected during home visits and scored by researchers blind to group assignment. The trial is registered on ClinicalTrials (NCT01187940, http://www.clinicaltrials.gov) and was funded by the Baily Thomas Charitable Trust. Results Bootstrap multiple regression showed ASD knowledge (β = .29, p

Glioblastoma is the most common and aggressive histologic subtype of brain cancer with poor outcomes and limited treatment options. Here, we report the selective overexpression of the protein arginine methyltransferase PRMT5 as a novel candidate theranostic target in this disease. PRMT5 silences the transcription of regulatory genes by catalyzing symmetric dimethylation of arginine residues on histone tails. PRMT5 overexpression in patient-derived primary tumors and cell lines correlated with cell line growth rate and inversely with overall patient survival. Genetic attenuation of PRMT5 led to cell-cycle arrest, apoptosis, and loss of cell migratory activity. Cell death was p53-independent but caspase-dependent and enhanced with temozolomide, a chemotherapeutic agent used as a present standard of care. Global gene profiling and chromatin immunoprecipitation identified the tumor suppressor ST7 as a key gene silenced by PRMT5. Diminished ST7 expression was associated with reduced patient survival. PRMT5 attenuation limited PRMT5 recruitment to the ST7 promoter, led to restored expression of ST7 and cell growth inhibition. Finally, PRMT5 attenuation enhanced glioblastoma cell survival in a mouse xenograft model of aggressive glioblastoma. Together, our findings defined PRMT5 as a candidate prognostic factor and therapeutic target in glioblastoma, offering a preclinical justification for targeting PRMT5-driven oncogenic pathways in this deadly disease. Cancer Res; 74(6); 1752–65. ©2014 AACR.

OBJECTIVE: This article examines the form and function of spontaneous communication and outcome predictors in nonverbal children with autism following classroom-based intervention (Picture Exchange Communication System [PECS] training). METHOD: 84 children from 15 schools participated in a randomized controlled trial (RCT) of PECS (P. Howlin, R. K. Gordon, G. Pasco, A. Wade, & T. Charman, 2007). They were aged 4-10 years (73 boys). Primary outcome measure was naturalistic observation of communication in the classroom. Multilevel Poisson regression was used to test for intervention effects and outcome predictors. RESULTS: Spontaneous communication using picture cards, speech, or both increased significantly following training (rate ratio [RR] =1.90, 95% CI [1.46, 2.48], p < .001; RR = 1.77, 95% CI [1.35, 2.32], p < .001; RR = 3.74, 95% CI [2.19, 6.37], p < .001, respectively). Spontaneous communication to request objects significantly increased (RR = 2.17, 95% CI [1.75, 2.68], p < .001), but spontaneous requesting for social purposes did not (RR = 1.34, 95% CI [0.83, 2.18], p = .237). Only the effect on spontaneous speech persisted by follow-up (9 months later). Less severe baseline autism symptomatology (lower Autism Diagnosis Observation Schedule [ADOS] score; C. Lord et al., 2000) was associated with greater increase in spontaneous speech (RR = 0.90, 95% CI [0.83, 0.98], p = .011) and less severe baseline expressive language impairment (lower ADOS item A1 score), with larger increases in spontaneous use of speech and pictures together (RR = 0.62, 95% CI [0.44, 0.88], p = .008). CONCLUSION: Overall, PECS appeared to enhance children's spontaneous communication for instrumental requesting using pictures, speech, or a combination of both. Some effects of training were moderated by baseline factors. For example, PECS appears to have increased spontaneous speech in children who could talk a little at baseline.

Objective To estimate the cost and impact of a centrally-driven quality improvement initiative in four UK mental health communities. Methods Total costs in year 1 were identified using documentation, a staff survey, semi-structured interviews and discussion groups. Few outcome data were collected within the programme so thematic analysis was used to identify the programme's impact within its five broad underlying principles. Results The survey had a 40% response. Total costs ranged between £164,000 and £458,000 per site, plus staff time spent on workstreams. There was a very hazy view of the resources absorbed and poor recording of expenditure and activity. The initiative generated little demonstrable improvements in service quality but some participants reported changes in attitudes. Conclusions Given the difficult contexts, short time-scales and capacity constraints, the programme's lack of impact is not surprising. It may, however, represent a worthwhile investment in cultural change which might facilitate improvements in how services are delivered.

In 1958, a field survey on the west coast of Islay produced a series of artefacts which suggest that there had been a rich female Viking burial on the site. Possible grave goods included two oval brooches, beads, spindle whorl, knives, sickle and the socket of a weaving batten. An ornamental buckle loop found at the site in 1978 may also belong to the grave, which appears to date to the late-ninth or tenth century AD. Au

Objective: To assess the effectiveness of expert training and consultancy for teachers of children with autism spectrum disorder in the use of the Picture Exchange Communication System (PECS). Method: Design: Group randomised, controlled trial (3 groups: immediate treatment, delayed treatment, no treatment). Participants: 84 elementary school children, mean age 6.8 years. Treatment: A 2-day PECS workshop for teachers plus 6 half-day, school-based training sessions with expert consultants over 5 months. Outcome measures: Rates of: communicative initiations, use of PECS, and speech in the classroom; Autism Diagnostic Observation Schedule-Generic (ADOS-G) domain scores for Communication and Reciprocal Social Interaction; scores on formal language tests. Results: Controlling for baseline age, developmental quotient (DQ) and language; rates of initiations and PECS usage increased significantly immediately post-treatment (Odds Ratio (OR) of being in a higher ordinal rate category 2.72, 95% confidence interval 1.22–6.09, p