Rapid review on safeguarding to inform the Healthy Child Programme 5 to 19

This is the final version of the article. Available from PHE Publications via the DOI in this recordSummary of key points 1. The purpose of this rapid review is to update the evidence in relation to safeguarding guidance in the Healthy Child Programme for 5 to 19 year-olds. 2. It synthesises evidence about ‘what works’ in prevention and early intervention as regards child abuse and neglect, child sexual abuse and exploitation, intimate partner violence (IPV), female genital mutilation (FGM) and gang violence. 3. Focusing on the period 2006 to 2015, a total of 27 systematic reviews and 9 additional randomised controlled trials (RCTs) are included. 4. Key messages on identifying families in need of additional support, the effective implementation of interventions, and workforce skills and training are also included, as is evidence on the economic aspects of safeguarding

What works to increase charitable donations? A meta-review with meta-meta-analysis

Many charities rely on donations to support their work addressing some of the world’s most pressing problems. We conducted a meta-review to determine what interventions work to increase charitable donations. We found 21 systematic reviews incorporating 1339 primary studies and over 2,139,938 participants. Our meta-meta-analysis estimated the average effect of an intervention on charitable donation size and incidence: r = 0.08 (95% CI [0.03, 0.12]). Due to limitations in the included systematic reviews, we are not certain this estimate reflects the true overall effect size. The most robust evidence found suggests charities could increase donations by (1) emphasising individual beneficiaries, (2) increasing the visibility of donations, (3) describing the impact of the donation, and (4) enacting or promoting tax-deductibility of the charity. We make recommendations for improving primary research and reviews about charitable donations, and how to apply the meta-review findings to increase charitable donations

The effectiveness of the Inspiring Futures parenting programme in improving behavioural and emotional outcomes in primary school children with behavioural or emotional difficulties: study protocol for a randomised controlled trial.

textabstractBackground: There is a need to build the evidence base of early interventions promoting children's health and development in the UK. Malachi Specialist Family Support Services ('Malachi') is a voluntary sector organisation based in the UK that delivers a therapeutic parenting group programme called Inspiring Futures to parents of children identified as having behavioural and emotional difficulties. The programme comprises two parts, delivered sequentially: (1) a group-based programme for all parents for 10-12 weeks, and (2) one-to-one sessions with selected parents from the group-based element for up to 12 weeks. Methods/design: A randomised controlled trial will be conducted to evaluate Malachi's Inspiring Futures parenting programme. Participants will be allocated to one of two possible arms, with follow-up measures at 16 weeks (post-parent group programme) and at 32 weeks (post-one-to-one sessions with selected parents). The sample size is 248 participants with a randomisation allocation ratio of 1:1. The intervention arm will be offered the Inspiring Futures programme. The control group will receive services as usual. The aim is to determine the effectiveness of the Inspiring Futures programme on the primary outcome of behavioural and emotional difficulties of primary school children identified as having behavioural or emotional difficulties. Discussion: This study will further enhance the evidence for early intervention parenting programmes for child behavioural and emotional problems in the UK

A Survey of New Temperature-Sensitive, Embryonic-Lethal Mutations in C. elegans: 24 Alleles of Thirteen Genes

To study essential maternal gene requirements in the early C. elegans embryo, we have screened for temperature-sensitive, embryonic lethal mutations in an effort to bypass essential zygotic requirements for such genes during larval and adult germline development. With conditional alleles, multiple essential requirements can be examined by shifting at different times from the permissive temperature of 15°C to the restrictive temperature of 26°C. Here we describe 24 conditional mutations that affect 13 different loci and report the identity of the gene mutations responsible for the conditional lethality in 22 of the mutants. All but four are mis-sense mutations, with two mutations affecting splice sites, another creating an in-frame deletion, and one creating a premature stop codon. Almost all of the mis-sense mutations affect residues conserved in orthologs, and thus may be useful for engineering conditional mutations in other organisms. We find that 62% of the mutants display additional phenotypes when shifted to the restrictive temperature as L1 larvae, in addition to causing embryonic lethality after L4 upshifts. Remarkably, we also found that 13 out of the 24 mutations appear to be fast-acting, making them particularly useful for careful dissection of multiple essential requirements. Our findings highlight the value of C. elegans for identifying useful temperature-sensitive mutations in essential genes, and provide new insights into the requirements for some of the affected loci

The Atypical Calpains: Evolutionary Analyses and Roles in Caenorhabditis elegans Cellular Degeneration

The calpains are physiologically important Ca2+-activated regulatory proteases, which are divided into typical or atypical sub-families based on constituent domains. Both sub-families are present in mammals, but our understanding of calpain function is based primarily on typical sub-family members. Here, we take advantage of the model organism Caenorhabditis elegans, which expresses only atypical calpains, to extend our knowledge of the phylogenetic evolution and function of calpains. We provide evidence that a typical human calpain protein with a penta EF hand, detected using custom profile hidden Markov models, is conserved in ancient metazoans and a divergent clade. These analyses also provide evidence for the lineage-specific loss of typical calpain genes in C. elegans and Ciona, and they reveal that many calpain-like genes lack an intact catalytic triad. Given the association between the dysregulation of typical calpains and human degenerative pathologies, we explored the phenotypes, expression profiles, and consequences of inappropriate reduction or activation of C. elegans atypical calpains. These studies show that the atypical calpain gene, clp-1, contributes to muscle degeneration and reveal that clp-1 activity is sensitive to genetic manipulation of [Ca2+]i. We show that CLP-1 localizes to sarcomeric sub-structures, but is excluded from dense bodies (Z-disks). We find that the muscle degeneration observed in a C. elegans model of dystrophin-based muscular dystrophy can be suppressed by clp-1 inactivation and that nemadipine-A inhibition of the EGL-19 calcium channel reveals that Ca2+ dysfunction underlies the C. elegans MyoD model of myopathy. Taken together, our analyses highlight the roles of calcium dysregulation and CLP-1 in muscle myopathies and suggest that the atypical calpains could retain conserved roles in myofilament turnover

What works to increase charitable donations? A meta-review with meta-meta-analysis

Many charities rely on donations to support their work addressing some of the world’s most pressing problems. We conducted a meta-review to determine what interventions work to increase charitable donations. We found 21 systematic reviews incorporating 1,339 primary studies and over 2,139,938 participants. Our meta-meta-analysis estimated the average effect of an intervention on charitable donation size and incidence: r = 0.08 (95% CI [0.03, 0.12]). Due to limitations in the included systematic reviews, we are not certain this estimate reflects the true overall effect size. The most robust evidence found suggests charities could increase donations by (1) emphasising individual beneficiaries, (2) increasing the visibility of donations, (3) describing the impact of the donation, and (4) enacting or promoting tax-deductibility of the charity. We make recommendations for improving primary research and reviews about charitable donations, and how to apply the meta-review findings to increase charitable donations

Measuring the Benefits of Entrepreneurship at Different Levels of Analysis

This paper presents a suggested framework for future research designs to examine the benefits of entrepreneurship, both non-financial and financial. Based on a review of the literature, and using contextual exemplars throughout the paper with an Australia and New Zealand focus, we identify a range of benefits from entrepreneurship at the various levels of analysis (e.g. individual, organizational, national). From a non-financial perspective such benefits include independence, autonomy, competitive advantage, increased market share, employment, and increased standards of living. From a financial perspective, entrepreneurship’s benefits include enhanced remuneration or rent from revenue, profits, cash flow, return on investment, and increases in GDP – specific financial measures to be expressed in clear financial terms. The suggested framework represents both an initial step towards the measurement of entrepreneurship’s financial benefits, and a valuable starting point for the development of a theory of the non-financial and financial benefits of entrepreneurship