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

The effectiveness of a therapeutic parenting program for children aged 6-11 years with behavioral or emotional difficulties: Results from a randomised controlled trial

Objective The aim of the study was to evaluate the implementation and effectiveness of a therapeutic parenting program that targets parents of children aged 6 to 11 years identified as having behavioral and emotional difficulties. The intervention comprises two parts, delivered sequentially: a 10–12-week group-based program for all parents, and one-to-one sessions for up to 12 weeks with selected parents from the group-based element. Methods/Design In a randomized controlled trial, 264 participants were allocated to the Inspiring Futures program (intervention) or services as usual (control) arms with follow-up assessments at 16 (post-group program) and 32 (post-one-to-one sessions) weeks. The primary outcome was the parent-rated Strengths and Difficulties Questionnaire (SDQ) Total Difficulties score at 32 weeks. Secondary outcomes included parent-rated SDQ subscales, parent coping strategies, empathy in parenting and parenting skills. Results All 264 participants were included in outcome analyses. There was no statistically significant effect on SDQ Total Difficulties (standardized mean difference: −0.07; 95% CI: −0.30 to 0.16; p = 0.54). There were no sub-group effects. Only 1 of 40 comparisons between the trial arms for secondary outcomes across both follow-ups was statistically significant at the 5% level. The mean number of group sessions attended by intervention arm participants was 6.1 (out of 10 to 12) and only 1 in 20 intervention arm participants received one-to-one support. Independent observation indicated scope to improve fidelity in terms of adherence, quality and participant responsiveness. Conclusions The intervention is not more effective than services as usual at improving targeted outcomes. This may be related, in part, to implementation issues but arguably more to the inability of a non-behavioral intervention to improve caregiving adequately, particularly when it is not targeted at new parents who have experienced trauma or deprivation early in life or subsequently

Toward Bifunctional Chelators for Thallium-201 for Use in Nuclear Medicine

[Image: see text] Auger electron therapy exploits the cytotoxicity of low-energy electrons emitted during radioactive decay that travel very short distances (typically <1 μm). (201)Tl, with a half-life of 73 h, emits ∼37 Auger and other secondary electrons per decay and can be tracked in vivo as its gamma emissions enable SPECT imaging. Despite the useful nuclear properties of (201)Tl, satisfactory bifunctional chelators to incorporate it into bioconjugates for molecular targeting have not been developed. H(4)pypa, H(5)decapa, H(4)neunpa-NH(2), and H(4)noneunpa are multidentate N- and O-donor chelators that have previously been shown to have high affinity for (111)In, (177)Lu, and (89)Zr. Herein, we report the synthesis and serum stability of [(nat/201)Tl]Tl(3+) complexes with H(4)pypa, H(5)decapa, H(4)neunpa-NH(2), and H(4)noneunpa. All ligands quickly and efficiently formed complexes with [(201)Tl]Tl(3+) that gave simple single-peak radiochromatograms and showed greatly improved serum stability compared to DOTA and DTPA. [(nat)Tl]Tl-pypa was further characterized using nuclear magnetic resonance spectroscopy (NMR), mass spectroscopy (MS), and X-ray crystallography, showing evidence of the proton-dependent presence of a nine-coordinate complex and an eight-coordinate complex with a pendant carboxylic acid group. A prostate-specific membrane antigen (PSMA)-targeting bioconjugate of H(4)pypa was synthesized and radiolabeled. The uptake of [(201)Tl]Tl-pypa-PSMA in DU145 PSMA-positive and PSMA-negative prostate cancer cells was evaluated in vitro and showed evidence of bioreductive release of (201)Tl and cellular uptake characteristic of unchelated [(201)Tl]TlCl. SPECT/CT imaging was used to probe the in vivo biodistribution and stability of [(201)Tl]Tl-pypa-PSMA. In healthy animals, [(201)Tl]Tl-pypa-PSMA did not show the myocardial uptake that is characteristic of unchelated (201)Tl. In mice bearing DU145 PSMA-positive and PSMA-negative prostate cancer xenografts, the uptake of [(201)Tl]Tl-pypa-PSMA in DU145 PSMA-positive tumors was higher than that in DU145 PSMA-negative tumors but insufficient for useful tumor targeting. We conclude that H(4)pypa and related ligands represent an advance compared to conventional radiometal chelators such as DOTA and DTPA for Tl(3+) chelation but do not resist dissociation for long periods in the biological environment due to vulnerability to reduction of Tl(3+) and subsequent release of Tl(+). However, this is the first report describing the incorporation of [(201)Tl]Tl(3+) into a chelator–peptide bioconjugate and represents a significant advance in the field of (201)Tl-based radiopharmaceuticals. The design of the next generation of chelators must include features to mitigate this susceptibility to bioreduction, which does not arise for other trivalent heavy radiometals

Partnership concurrency and coital frequency.

National HIV prevalence estimates across sub-Saharan Africa range from less than 1 percent to over 25 percent. Recent research proposes several explanations for the observed variation, including prevalence of male circumcision, levels of condom use, presence of other sexually transmitted infections, and practice of multiple concurrent partnerships. However, the importance of partnership concurrency for HIV transmission may depend on how it affects coital frequency with each partner. The coital dilution hypothesis suggests that coital frequency within a partnership declines with the addition of concurrent partners. Using sexual behavior data from rural Malawi and urban Kenya, we investigate the relationship between partnership concurrency and coital frequency, and find partial support for the coital dilution hypothesis. We conclude the paper with a discussion of our findings in light of the current literature on concurrency

IgG4 subclass antibodies impair antitumor immunity in melanoma

Host-induced antibodies and their contributions to cancer inflammation are largely unexplored. IgG4 subclass antibodies are present in IL-10–driven Th2 immune responses in some inflammatory conditions. Since Th2-biased inflammation is a hallmark of tumor microenvironments, we investigated the presence and functional implications of IgG4 in malignant melanoma. Consistent with Th2 inflammation, CD22(+) B cells and IgG4(+)-infiltrating cells accumulated in tumors, and IL-10, IL-4, and tumor-reactive IgG4 were expressed in situ. When compared with B cells from patient lymph nodes and blood, tumor-associated B cells were polarized to produce IgG4. Secreted B cells increased VEGF and IgG4, and tumor cells enhanced IL-10 secretion in cocultures. Unlike IgG1, an engineered tumor antigen-specific IgG4 was ineffective in triggering effector cell–mediated tumor killing in vitro. Antigen-specific and nonspecific IgG4 inhibited IgG1-mediated tumoricidal functions. IgG4 blockade was mediated through reduction of FcγRI activation. Additionally, IgG4 significantly impaired the potency of tumoricidal IgG1 in a human melanoma xenograft mouse model. Furthermore, serum IgG4 was inversely correlated with patient survival. These findings suggest that IgG4 promoted by tumor-induced Th2-biased inflammation may restrict effector cell functions against tumors, providing a previously unexplored aspect of tumor-induced immune escape and a basis for biomarker development and patient-specific therapeutic approaches