The role of peroxisome proliferator activated receptor alpha (PPARα) in the effect of piroxicam on colon cancer

Studies with APCMin/+ mice and APCMin/+ PPARα-/- mice were undertaken to investigate whether polyp development in the mouse gut was mediated by PPARα. Additionally, the effect of piroxicam treatment dependency on PPARα was assessed. Results showed the number of polyps in the colon was significantly higher in APCMin/+ PPARα-/- mice than in APCMin/+ mice, whilst in the small bowel the difference was not significant. Analysis of gene expression in the colon with Affymetrix® microarrays demonstrated the largest source of variation was between tumour and normal tissue. Deletion of PPARα had little effect on gene expression in normal tissue but appeared to have more effect in tumour tissue. Ingenuity pathway analysis of these data showed the top biological processes were growth & proliferation and colorectal cancer. Collectively, these data may indicate that deletion of PPARα exacerbates the existing APCMin/+ mutation to promote tumorigenesis in the colon. 95 genes from Affymetrix® microarray data were selected for further analysis on Taqman® low density arrays. There was good correlation of expression levels between the two array types. Expression data of two genes proved particularly interesting; Onecut homeobox 2 (Onecut2) and Apolipoprotein B DNA dC dU - editing enzyme, catalytic polypeptide 3 (Apobec3). Onecut2 was highly up-regulated in tumour tissue. Apobec3 was up-regulated in APCMin/+ PPARα-/- mice only; suggesting expression was mediated via PPARα. There was a striking increase in survival accompanied by a marked reduction in small intestinal polyp numbers in mice of either genotype that received piroxicam. Taqman® low density array analysis of the same 95 genes as previously showed similar expression levels in piroxicam-treated APCMin/+ mice and APCMin/+ PPARα-/- mice. Taken together, these data indicated that the effect of piroxicam treatment was not mediated via PPARα

The role of peroxisome proliferator activated receptor alpha (PPARα) in the effect of piroxicam on colon cancer

Studies with APCMin/+ mice and APCMin/+ PPARα-/- mice were undertaken to investigate whether polyp development in the mouse gut was mediated by PPARα. Additionally, the effect of piroxicam treatment dependency on PPARα was assessed. Results showed the number of polyps in the colon was significantly higher in APCMin/+ PPARα-/- mice than in APCMin/+ mice, whilst in the small bowel the difference was not significant. Analysis of gene expression in the colon with Affymetrix® microarrays demonstrated the largest source of variation was between tumour and normal tissue. Deletion of PPARα had little effect on gene expression in normal tissue but appeared to have more effect in tumour tissue. Ingenuity pathway analysis of these data showed the top biological processes were growth & proliferation and colorectal cancer. Collectively, these data may indicate that deletion of PPARα exacerbates the existing APCMin/+ mutation to promote tumorigenesis in the colon. 95 genes from Affymetrix® microarray data were selected for further analysis on Taqman® low density arrays. There was good correlation of expression levels between the two array types. Expression data of two genes proved particularly interesting; Onecut homeobox 2 (Onecut2) and Apolipoprotein B DNA dC dU - editing enzyme, catalytic polypeptide 3 (Apobec3). Onecut2 was highly up-regulated in tumour tissue. Apobec3 was up-regulated in APCMin/+ PPARα-/- mice only; suggesting expression was mediated via PPARα. There was a striking increase in survival accompanied by a marked reduction in small intestinal polyp numbers in mice of either genotype that received piroxicam. Taqman® low density array analysis of the same 95 genes as previously showed similar expression levels in piroxicam-treated APCMin/+ mice and APCMin/+ PPARα-/- mice. Taken together, these data indicated that the effect of piroxicam treatment was not mediated via PPARα

A qualitative case study in the social capital of co-professional collaborative co-practice for children with speech language and communication needs

Background: Effective co-practice is essential to deliver services for children with speech language and communication needs (SLCN). The necessary skills, knowledge and resources are distributed amongst professionals and agencies. Co-practice is complex and a number of barriers, such as 'border disputes' and poor awareness of respective priorities, have been identified. However social-relational aspects of co-practice have not been explored in sufficient depth to make recommendations for improvements in policy and practice. Here we apply social capital theory to data from practitioners: an analytical framework with the potential to move beyond descriptions of socio-cultural phenomena to inform change.  Aims: Co-practice in a Local Authority site was examined to understand: 1) the range of social capital relations extant in the site’s co-practice; 2) how these relations affected the abilities of the network to collaborate; 3) whether previously identified barriers to copractice remain; 4) the nature of any new complexities which may have emerged; and 5) how inter-professional social capital might be fostered.  Methods & Procedures: A qualitative case study of SLCN provision within one Local Authority in England and its linked NHS partner was completed through face-to-face semistructured interviews with professionals working with children with SCLN across the authority. Interviews, exploring barriers and facilitators to interagency working and social capital themes, were transcribed, subjected to thematic analysis using iterative methods and a thematic framework derived.  Outcomes and Results: We identified a number of characteristics important for the effective development of trust, reciprocity and negotiated co-practice at different levels of social capital networks knowledge and skills. Barriers to co-practice differed from those found in earlier studies. Some negative aspects of complexity were evident but only where networked professionalism and trust was absent between professions. Where practitioners embraced and services and systems enabled more fluid forms of collaboration, then trust and reciprocity developed.  Conclusions & Implications: Highly collaborative forms of co-practice, inherently more complex at the service governance, macro-level, bring benefits. At the meso-level of the school and support team network there was greater capacity to individualise co-practice to the needs of the child. Capacity was increased at the micro-level of knowledge and skills to harness the overall resource distributed amongst members of the inter-professional team. The development of social capital, networks of trust across SLCN support teams, should be a priority at all levels - for practitioners, services, commissioners and schools

Variation in headteachers' approaches to meeting the needs of primary school children with speech, language and communication needs (SLCN) in one English Local Authority: a systems approach

Background Recent large-scale research in England has reported lack of equity in the school services and support received by children with speech, language and communication needs (SLCN), even in schools in similar demographic areas. How headteachers organise support for pupils with SLCN is considered important in determining their school experiences, but there is little research related to SLCN. The present study analysed the views of eight headteachers to illustrate variation across school systems as reported by heads. Aims The aim was to illustrate and exemplify the wide range of headteachers' views and variation across school systems, and their impact for pupils. Methods & Procedures The study analysed data from face-to-face, semi-structured interviews with eight volunteer headteachers in a large-scale qualitative study of co-working and services for primary school pupils with SLCN, the Language for All project, in one English local authority. Responses were analysed using a four-level systems model, considering each head's views of the SEND policy environment; whether SLCN was considered when setting school goals and prioritising functions; staff recruitment and staff skills relating to SLCN, and the processes whereby curriculum adaptations were planned and delivered. Following close reading, discussion and review of headteachers’ transcribed interviews, the research team classified statements under the systems components, with dissonance sought in line with the study's aim of identifying variation. Responses from four headteachers who reported fundamentally different views were selected for discussion, illustrated by quotations. Outcomes & Results Despite coming under the same authority and policy directives, the systems analysis showed considerable variation. For example, Headteachers One and Two differed markedly on their schools' reported goals/functions and structures, with resulting difference in educational processes. Headteachers Three and Four illustrated large differences in processes, particularly how language-learning activities were planned and delivered. There was variation around how heads managed SEND funds; whether SLCN was formally recognised as a school priority; the recruitment and training of staff with expertise in SLCN and their recognition at management level; and in the resulting experiences for children, including reliance on outside professionals. All heads recognised the need to support SLCN, and were spending time and effort to secure adequate provision. Nonetheless, the variation shown risked inequality. Conclusions & Implications The systems analysis proved useful analysis and clarification of school organisation that contributes to variation in child experiences. Headteachers were powerful influences on school systems, with further understandings of their views, roles and actions is needed

Co/productive practitioner relations for children with SLCN: an affect inflected agentic frame

This paper examines how school-based practitioners supporting children with speech, language and communication needs (SLCN) use particular social capital relations. Social capital theory together with selected ‘Productive Pedagogies’ items, are applied to re-frame and understand the co/production of support for such children. Empirical data from the ‘Language for All’ study, which investigates SLCN provision in schools in England, are analysed to understand support network social capital. Novel insights on the types and purposes of interprofessional connectedness within SLCN support networks, in particular how relational agency is inflected by affect, are offered

A national study to investigate the clinical use of standardised instruments in autism spectrum disorder assessment of children and adults in Scotland

Background - There are few large scale studies about the nature and extent of the actual use of standardised assessments for Autism Spectrum Disorder diagnosis in clinical practice. This study compares and contrasts practice in diagnostic services for both adults and children. Method - We conducted an analysis of retrospective case notes from 150 cases (70 adult, 80 children) assessed for Autism Spectrum Disorder by 16 diagnostic services. Results - We found differences between adult and child services in staff training and use of standardised assessment during diagnosis. All child services had staff trained in and regularly using standardised assessments. Most adult services had staff trained in using instruments but only half used them regularly. Administration of standardised ASD assessments was ten times more likely in children than in adults (OR = 10.1; CI = 4.24, 24.0). Child services selected the ADOS as the standardised tool and adult services selected the DISCO, with very little overlap. Decisions to administer standardised tools were not based on case complexity but rather the same process was applied to all referrals within a service. The three recommended components of assessment (clinical history, clinical observation and contextual information) were included for the majority of cases, although clinical observation was more frequently used with children than with adults. Conclusions - Based on the findings, we suggest a need for a wider range of appropriate assessments for use with adults, particularly those with an intellectual disability and for further research into the reasons behind the choices clinicians make during the assessment process. For child services in Scotland, there is a need for more training in use of current diagnostic interviews. Clinicians did not vary tools used based on complexity, suggesting that this is a notion still to be clearly defined and operationalised in clinical decision making about the use of standardised assessments

The Grizzly, September 4, 1987

Convocation Greets Academic Year • Eisenhower Speech Kicks off New Year • Land of the Rising Sun • Student Life Shapes Up • Letter: Just Call Me Papa Juan • Just When You Thought It was Safe • Garrick Joins Resident Director Program • Hiel Begins Boosting Bookstore • Hager Brings New Ideas to College • Quinlin Continues Education • Notes: Women\u27s Stress Workshop; U.C. Honors Hardman and Neslen • Ursinus Football: For the Sheer Fun of It • Cross Country Runs Towards Promising Season • Hockey Travel to West Chester for Annual Tournament • Tannenbaum Sweeps CoSIDA Awards Again • Soccer Off to Rocky Start • The Dead Will Survive • Oh No! Video Blowouthttps://digitalcommons.ursinus.edu/grizzlynews/1190/thumbnail.jp

Responding to global challenges in food, energy, environment and water: Risks and options assessment for decision-Making

We analyse the threats of global environmental change, as they relate to food security. First, we review three discourses: (i) ‘sustainable intensification’, or the increase of food supplies without compromising food producing inputs, such as soils and water; (ii) the ‘nexus’ that seeks to understand links across food, energy, environment and water systems; and (iii) ‘resilience thinking’ that focuses on how to ensure the critical capacities of food, energy and water systems are maintained in the presence of uncertainties and threats. Second, we build on these discourses to present the causal, risks and options assessment for decision-making process to improve decision-making in the presence of risks. The process provides a structured, but flexible, approach that moves from problem diagnosis to better risk-based decision-making and outcomes by responding to causal risks within and across food, energy, environment and water systems

Risk factors to predict the incidence of surgical adverse events following open or laparoscopic surgery for apparent early stage endometrial cancer: Results from a randomised controlled trial

Aims: To identify risk factors for major Adverse Events (AEs) and to develop a nomogram to predict the probability of such AEs in individual patients who have surgery for apparent early stage endometrial cancer. Methods: We used data from 753 patients who were randomized to either total laparoscopic hysterectomy or total abdominal hysterectomy in the LACE trial. Serious adverse events that prolonged hospital stay or postoperative adverse events (using common terminology criteria 3+, CTCAE V3) were considered major AEs. We analyzed pre-surgical characteristics that were associated with the risk of developing major AEs by multivariate logistic regression. We identified a parsimonious model by backward stepwise logistic regression. The six most significant or clinically important variables were included in the nomogram to predict the risk of major AEs within 6 weeks of surgery and the nomogram was internally validated. Results: Overall, 132 (17.5%) patients had at least one major AE. An open surgical approach (laparotomy), higher Charlson’s medical co-morbidities score, moderately differentiated tumours on curettings, higher baseline ECOG score, higher body mass index and low haemoglobin levels were associated with AE and were used in the nomogram. The bootstrap corrected concordance index of the nomogram was 0.63 and it showed good calibration. Conclusions: Six pre-surgical factors independently predicted the risk of major AEs. This research might form the basis to develop risk reduction strategies to minimize the risk of AEs among patients undergoing surgery for apparent early stage endometrial cancer

Multifactorial falls prevention programme compared with usual care in UK care homes for older people: Multicentre cluster randomised controlled trial with economic evaluation

Objectives: To determine the clinical and cost effectiveness of a multifactorial fall prevention programme compared with usual care in long term care homes. Design: Multicentre, parallel, cluster randomised controlled trial. Setting: Long term care homes in the UK, registered to care for older people or those with dementia. Participants: 1657 consenting residents and 84 care homes. 39 were randomised to the intervention group and 45 were randomised to usual care. Interventions: Guide to Action for Care Homes (GtACH): a multifactorial fall prevention programme or usual care. Main outcome measures: Primary outcome measure was fall rate at 91-180 days after randomisation. The economic evaluation measured health related quality of life using quality adjusted life years (QALYs) derived from the five domain five level version of the EuroQoL index (EQ-5D-5L) or proxy version (EQ-5D-5L-P) and the Dementia Quality of Life utility measure (DEMQOL-U), which were self-completed by competent residents and by a care home staff member proxy (DEMQOL-P-U) for all residents (in case the ability to complete changed during the study) until 12 months after randomisation. Secondary outcome measures were falls at 1-90, 181-270, and 271-360 days after randomisation, Barthel index score, and the Physical Activity Measure-Residential Care Homes (PAM-RC) score at 91, 180, 270, and 360 days after randomisation. Results: Mean age of residents was 85 years. 32% were men. GtACH training was delivered to 1051/1480 staff (71%). Primary outcome data were available for 630 participants in the GtACH group and 712 in the usual care group. The unadjusted incidence rate ratio for falls between 91 and 180 days was 0.57 (95% confidence interval 0.45 to 0.71, P<0.001) in favour of the GtACH programme (GtACH: six falls/1000 residents v usual care: 10 falls/1000). Barthel activities of daily living indices and PAM-RC scores were similar between groups at all time points. The incremental cost was £108 (95% confidence interval −£271.06 to 487.58), incremental QALYs gained for EQ-5D-5L-P was 0.024 (95% confidence interval 0.004 to 0.044) and for DEMQOL-P-U was 0.005 (−0.019 to 0.03). The incremental costs per EQ-5D-5L-P and DEMQOL-P-U based QALY were £4544 and £20 889, respectively. Conclusions: The GtACH programme was associated with a reduction in fall rate and cost effectiveness, without a decrease in activity or increase in dependency. Trial registration: ISRCTN34353836