Growing Pains: Getting past the complexities of scaling social impact

In communities across the UK, organisations develop new ideas to improve the lives of those around them. And yet despite growing demand for charity services, concerted attempts to take proven approaches to scale are few and far between, and successful examples are rarer still. This paper aims to bring about a change in tack by proposing a way of assessing the viability of scaling in different contexts

Early Interventions: An Economic Approach to Charitable Giving

This report highlights the estimated £100bn combined cost impact of some of the most difficult social issues and looks at how private funders can help tackle the root causes of these issues, and in turn deliver significant savings to state and help individual lives. It identifies that early intervention is key to tackling serious social issues which can later become entrenched, therefore bringing significant cost savings to state finances

Best to Invest? A Funders' Guide to Social Investment

Social investment offers the opportunity for socially-minded investors to increase the impact of their money. It's still early days, but already the concept has attracted much interest from funders and has the potential to help charities access long-term, affordable finance. In Best to invest? A new social investment guide for funders published today, NPC finds that the crucial 'next wave' of potential funders are being put off by the perceived complexity of social investment. People interested in social investment are being deterred, as it can be challenging to value accurately social investments in terms of the likely social and financial risk and return; the legal structures involved are complex and often bespoke for each investment; and it can be difficult to obtain investment advice, which is regulated by the Financial Conduct Authority (FCA). The final barrier identified is that investment decisions tend to be outsourced to professionals who are not comfortable or familiar with the blending of the financial goals of investment with the social goals of grant-making. However, interest in social investment among funders is growing. In a time of spending cuts and austerity, many funders are seeing increasing demand for their funding to pay for services previously supported by government contracts or public donations. At the same time, many trusts and foundations have seen the return on their investments dwindle, making it harder to sustain their grant-making. In this context, social investment is an attractive prospect for funders who want to do more to support charities and social enterprises, in a way that has the potential to make both more sustainable in the long term

Activity Schedules for Children with Severe Diagnoses: Teaching Independent Play in the Absence of Adult Prompting

Abstract Children diagnosed with severe intellectual disabilities (ID) and autism spectrum disorders (ASD) often lack independence, relying on adult prompting to engage in play activities. In the absence of adult prompting or access to reinforcers (R+), independent engagement typically does not occur. Activity schedule (AS) interventions have been successfully implemented to develop a wide range of skills in this population, but many AS studies incorporated additional prompts and therefore do not adhere to the original protocol designed by MacDuff et al. (1993), named here as PCDI-AS. While other methods have been successful, it is not clear if adding gestural and/or verbal prompting improves effectiveness. To investigate the effectiveness of PCDI-AS and AS using other methods for individuals diagnosed with severe ID and/or ASD, two studies were completed: Study One - Systematic Review: Aims. To a) to systematically assess both effectiveness and quality of all studies using AS with participants with ID or ASD, and compare results of PCDI-AS versus AS using other methods, and b) provide a narrative synthesis of all studies with a focus on interventions designed to develop independent play skills. Method. A systematic review was conducted, including a narrative synthesis. Each study was assessed for quality using the single case experimental design (SCED) scale (Tate, McDonald, Perdices, Togher, Schultz & Savage, 2008). The percentage of non-overlapping data (PND) method was used to estimate effect size (Scruggs, Mastropieri & Casto, 1997). Results. Comparison of both quality and effectiveness data indicate that while AS are moderately effective, the PCDI-AS approach is highly effective. PCDI-AS evidenced more generalisation than AS using other methods. While only one study implemented PCDI-AS to develop independent play skills in those with severe diagnoses, results indicate it was effective Conclusion: Findings are limited to use of PND and SCED as measurement systems, as other measurement systems may have yielded different results, however, data collected via these methods suggest that for developing independent play skills in those with ID and/or ASD diagnoses PDI-AS is more suitable than AS using other methods. Study Two - Intervention: Aims. To a) identify if PCDI-AS are suitable for teaching engagement with play materials to individuals with severe ASD or ID, in the absence of adult prompting, and b) to see if skills acquired during training would generalise to other settings under the control of naturally occurring stimuli. Method. Following pre-requisite skill training, PCDI-AS was introduced, at different time points, to a cohort of 9 pupils presenting with ID and/or ASD within the severe range. To measure the effect of PCDI-AS on independent engagement with play materials in another setting, for each individual, different aspects of play skills were measured during child-initiated play sessions both prior to and during the intervention. Data were compiled to create non-concurrent multiple baseline across participants designs. Results. PCDI-AS appears to be effective for developing independent play skills in participants with severe diagnoses; six pupils mastered schedule following. Play observations suggested that PCDI-AS impacted upon behaviour in other settings. Following the start of training, for most, levels of engagement increased and variety of play materials widened. Conclusion: The current study is limited to 9 pupils in one location, therefore, results must be interpreted with caution. However it has significance for pupils with severe diagnoses who are prompt dependent and lack independent play skills, and for those professionals who seek to develop their skills. Discussion While AS are effective in general, the systematic review suggests that PCDI-AS are more effective than AS using other methods, and are associated with more generalisation. To develop their independent play skills, pupils with severe diagnoses were introduced to PCDI-AS. The intervention appeared to be successful; independent schedule following occurred under the stimulus control of visual cues alone, in the absence of adult prompting. Furthermore, evidence suggested that skills can be generalised to other settings under the control of naturally occurring stimuli

Structural and physiological neurovascular changes in idiopathic Parkinson's disease and its clinical phenotypes

Neurovascular changes are likely to interact importantly with the neurodegenerative process in idiopathic Parkinson's disease (IPD). Markers of neurovascular status (NVS) include white matter lesion (WML) burden and arterial spin labelling (ASL) measurements of cerebral blood flow (CBF) and arterial arrival time (AAT). We investigated NVS in IPD, including an analysis of IPD clinical phenotypes, by comparison with two control groups, one with a history of clinical cerebrovascular disease (CVD) (control positive, CP) and one without CVD (control negative, CN). Fifty-one patients with IPD (mean age 69.0 ± 7.7 years) (21 tremor dominant (TD), 24 postural instability and gait disorder (PIGD) and six intermediates), 18 CP (mean age 70.1 ± 8.0 years) and 34 CN subjects (mean age 67.4 ± 7.6 years) completed a 3T MRI scan protocol including T2-weighted fluid-attenuated inversion recovery (FLAIR) and ASL. IPD patients showed diffuse regions of significantly prolonged AAT, small regions of lower CBF and greater WML burden by comparison with CN subjects. TD patients showed lower WML volume by comparison with PIGD patients. These imaging data thus show altered NVS in IPD, with some evidence for IPD phenotype-specific differences

EPICOG-SCH: A brief battery to screen cognitive impact of schizophrenia in stable outpatients

Brief batteries in schizophrenia, are needed to screen for the cognitive impact of schizophrenia. We aimed to validate and co-norm the Epidemiological Study of Cognitive Impairment in Schizophrenia (EPICOG-SCH) derived brief cognitive battery. A cross-sectional outpatient evaluation was conducted of six-hundred-seventy-two patients recruited from 234 centers. The brief battery included well-known subtests available worldwide that cover cognitive domains related to functional outcomes: WAIS-III-Letter-Number-Sequencing-LNS, Category Fluency Test-CFT, Logical-Memory Immediate Recall-LM, and Digit-Symbol-Coding-DSC. CGI-SCH Severity and WHO-DAS-S were used to assess clinical severity and functional impairment, respectively. Unit Composite Score (UCS) and functional regression-weighted Composite Scores (FWCS) were obtained; discriminant properties of FWCS to identify patients with different levels of functional disability were analyzed using receiver-operating characteristic (ROC) technique. The battery showed good internal consistency, Cronbach's alpha = 0.78. The differences between cognitive performance across CGI-SCH severity level subscales ranged from 0.5 to 1 SD. Discriminant capacity of the battery in identifying patients with up to moderate disability levels showed fair discriminant accuracy with areas under the curve (AUC) > 0.70, p < 0.0001. An FWCS mean cut-off score ≥ 100 showed likelihood ratios (LR) up to 4.7, with an LR+ of 2.3 and a LR− of 0.5. An FWCS cut-off ≥ 96 provided the best balance between sensitivity (0.74) and specificity (0.62). The EPICOG-SCH proved to be a useful brief tool to screen for the cognitive impact of schizophrenia, and its regression-weighted Composite Score was an efficient complement to clinical interviews for confirming patients' potential functional outcomes and can be useful for monitoring cognition during routine outpatient follow-up visits

The ERBB network facilitates KRAS-driven lung tumorigenesis

KRAS is the most frequently mutated driver oncogene in human adenocarcinoma of the lung. There are presently no clinically proven strategies for treatment of KRAS-driven lung cancer. Activating mutations in KRAS are thought to confer independence from upstream signaling; however, recent data suggest that this independence may not be absolute. We show that initiation and progression of KRAS-driven lung tumors require input from ERBB family receptor tyrosine kinases (RTKs): Multiple ERBB RTKs are expressed and active from the earliest stages of KRAS-driven lung tumor development, and treatment with a multi-ERBB inhibitor suppresses formation of KRASG12D-driven lung tumors. We present evidence that ERBB activity amplifies signaling through the core RAS pathway, supporting proliferation of KRAS-mutant tumor cells in culture and progression to invasive disease in vivo. Brief pharmacological inhibition of the ERBB network enhances the therapeutic benefit of MEK (mitogen-activated protein kinase kinase) inhibition in an autochthonous tumor setting. Our data suggest that lung cancer patients with KRAS-driven disease may benefit from inclusion of multi-ERBB inhibitors in rationally designed treatment strategies

Blood-brain barrier leakage is increased in Parkinson’s disease

Background: Blood-brain barrier disruption has been noted in animal models of Parkinson’s disease (PD) and forms the basis of the vascular hypothesis of neurodegeneration, yet clinical studies are lacking. Objective: To determine alterations in blood-brain barrier integrity in PD, with comparison to cerebrovascular disease. Methods: Dynamic contrast enhanced magnetic resonance images were collected from 49 PD patients, 15 control subjects with cerebrovascular disease (control positive CP) and 31 healthy control subjects (control negative CN), with all groups matched for age. Quantitative maps of the contrast-agent transfer coefficient across the blood-brain barrier (Ktrans) and plasma volume (vp) were produced using Patlak analysis. Differences in Ktrans and vp were assessed with voxel-based analysis as well as in regions associated with PD pathophysiology. In addition, the volume of white matter lesions (WML) was obtained from T2-weighted fluid attenuation inversion recovery (FLAIR) images. Results: Higher Ktrans, reflecting higher blood-brain barrier leakage, was found in the PD group than in the CN group using voxel-based analysis; differences were most prominent in the posterior white matter regions. Region of interest analysis confirmed Ktrans to be significantly higher in PD than in CN, predominantly driven by differences in the substantia nigra, normal-appearing white matter, WML and the posterior cortex. WML volume was significantly higher in PD compared to CN. Ktrans values and white matter lesion volume were similar in PD and CP, suggesting a similar burden of cerebrovascular disease despite lower cardiovascular risk factors. Conclusion: These results show blood-brain barrier disruption in PD

Diversity of woody-host infecting Phytophthora species in public parks and botanic gardens as revealed by metabarcoding, and opportunities for mitigation through best practice

The diversity of Phytophthora species in soils collected from 14 highly disturbed sites in northern Britain, including botanic gardens, arboreta, public parks and other amenity woodland sites, was analysed using a molecular technique known as DNA metabarcoding. This technique enables the identification of multiple species present in a single environmental sample based on a DNA ‘barcode’ unique to each species. The genus Phytophthora was targeted in this study due to its increasing impact on Britain’s forests and woodlands over thelast 20 years. The introduction and spread of new Phytophthora species into Britain has been strongly associated with the movement of traded containerised plants, with a number of Phytophthora outbreaks reported on host trees located in public gardens and parks that had recently undergone planting or landscape regeneration schemes. This study was undertaken to assess the extent to which these highly disturbed sites with extensive planting regimes act as harbours for woody-host infecting Phytophthora species. A total of 23 Phytophthora species, the majority of which are known to be pathogens of woody hosts, were detected across the 14 sites sampled. These included four quarantine-regulated pathogens and four species notpreviously recorded in Britain. Also detected were three as-yet undescribed Phytophthora species and nine oomycete sequences with no clear match to any known genus. There was no effect of geographical location, elevation, underlying soil type, host family or host health status on the Phytophthora assemblages at each site, suggesting that the Phytophthora communities detected are likely to comprise introduced species associated with planting programmes. P. austrocedri and P. pseudosyringae were two of the most abundant Phytophthoraspecies detected, both of which cause serious damage to trees and are regarded as fairly recent introductions to Britain. The practical implications of the findings in terms of mitigating Phytophthora introduction, spread and impact at botanic gardens, arboreta and urban parks are discussed

Improved thyroid hypoechogenicity following bariatric-induced weight loss in euthyroid adults with severe Obesity-a pilot study

Background: Obesity may affect both biochemical thyroid function tests; and thyroid morphology, as assessed using ultrasound scans (US). The aim of the present pilot study was to explore whether weight loss achieved by bariatric surgery alters thyroid US morphology including gray-scale measurements; and/or function in euthyroid adults with severe obesity. Methods: Euthyroid adults (> 18 years) with body mass index (BMI) ≥40 kg/m2 and negative thyroid peroxidase antibodies were assessed at baseline (pre-surgery) and after achieving at least 5% weight loss of their baseline body weight following bariatric surgery. Anthropometric assessments, biochemical/hormonal measurements (TSH, free-T4, free-T3, reverse-T3, and leptin) and thyroid US with gray-scale histogram analysis were performed at the baseline and post-surgery follow-up. Results: Ten Caucasian, euthyroid patients (women/men: 8/2; age: 48.6 ± 3.1 years; BMI: 51.4 ± 1.8 kg/m2) successfully completed this study with significantly decreased body weight (> 5% weight loss), waist circumference and serum leptin levels post-surgery (mean post-surgery follow-up duration: 16.5 ± 2.5 months). In parallel to the observed bariatric-induced weight loss, thyroid US echogenicity increased by 25% (p = 0.03), without significant changes in thyroid volume. No significant changes in thyroid function tests were detected. No significant correlations were observed between the increase in thyroid echogenicity and the decreases in anthropometric parameters and circulating leptin. Conclusion: Our results indicate that in euthyroid adults with severe obesity, marked weight loss achieved by bariatric surgery is associated with a parallel significant increase in the thyroid US echogenicity, suggesting that morphological changes of the thyroid in obesity are reversible with weight loss