Spontaneous and cued gaze-following in autism and Williams syndrome

Background: From a young age the typical development of social functioning relies upon the allocation of attention to socially relevant information, which in turn allows experience at processing such information and thus enhances social cognition. As such, research has attempted to identify the developmental processes that are derailed in some neuro-developmental disorders that impact upon social functioning. Williams syndrome (WS) and Autism are disorders of development that are characterized by atypical yet divergent social phenotypes and atypicalities of attention to people.

Methods: We used eye tracking to explore how individuals with WS and Autism attended to, and subsequently interpreted, an actor’s eye gaze cue within a social scene. Images were presented for three seconds, initially with an instruction simply to look at the picture. The images were then shown again, with the participant asked to identify the object being looked at. Allocation of eye-gaze in each condition was analyzed by ANOVA and accuracy of identification was compared with t-tests.

Results: Participants with WS allocated more gaze time to face and eyes than their matched controls both with and without being asked to identify the item being looked at; while participants with Autism spent less time on face and eyes in both conditions. When cued to follow gaze, participants with WS increased gaze to the correct targets, while those with Autism looked more at the face and eyes but did not increase gaze to the correct targets, while continuing to look much more than their controls at implausible targets. Both groups identified fewer objects than their controls.

Conclusions: The atypicalities found are likely to be entwined with the deficits shown in interpreting social cognitive cues from the images. WS and Autism are characterised by atypicalities of social attention that impact upon socio-cognitive expertise but importantly the type of atypicality is syndrome-specific.

Defining the molecular basis for the first potent and selective orthosteric agonists of the FFA2 free fatty acid receptor

FFA2 is a G protein-coupled receptor that responds to short chain fatty acids (SCFAs) and has generated interest as a therapeutic target for metabolic and inflammatory conditions. However, definition of its functions has been slowed by a dearth of selective ligands that can distinguish it from the closely related FFA3. At present, the only selective ligands described for FFA2 suffer from either poor potency, altered signaling due to allosteric modes of action, or a lack of function at non-human orthologs of the receptor. To address the need for novel selective ligands, we synthesized two compounds potentially having FFA2 activity and examined the molecular basis of their function. These compounds were confirmed to be potent and selective FFA2 agonists that interact with the orthosteric binding site. A combination of ligand structure-activity relationship, pharmacological analysis, homology modeling, species ortholog comparisons and mutagenesis studies were then employed to define the molecular basis of selectivity and function of these ligands. From this, we identified key residues within both extracellular loop 2 (ECL2) and the transmembrane domain (TM) regions of FFA2 critical for ligand function. One of these ligands was active with reasonable potency at rodent orthologs of FFA2 and demonstrated the role of FFA2 in the regulation of lipolysis in murine 3T3-L1 adipocytes. Together, these findings describe the first potent and selective FFA2 orthosteric agonists and demonstrate key aspects of ligand interaction within the orthosteric binding site of FFA2 that will be invaluable in future ligand development at this receptor.

Novel synthetic route to the C-nucleoside, 2-deoxy benzamide riboside

2-Deoxy-C-nucleosides are a subcategory of C-nucleosides that has not been explored extensively, largely because the synthesis is less facile. Flexible synthetic procedures giving access to 2-deoxy-C-nucleosides are therefore of interest. To exemplify the versatility and highlight the limitations of a synthetic route recently developed to that effect, the first synthesis of 2-deoxy benzamide riboside is reported. Biological properties of this novel C-nucleoside are also discussed. (c) 2012 Elsevier Ltd. All rights reserved.

Surveillance of severe chemical corneal injuries in the UK

AIM: To estimate the incidence of severe chemical corneal injuries in the UK and describe presenting clinical features and initial management.

METHODS: All patients with severe chemical corneal injury in the UK from December 2005 to November 2006 inclusive were prospectively identified using the British Ophthalmological Surveillance Unit. Reporting ophthalmologists provided information regarding presentation and follow-up.

RESULTS: Twelve cases were identified, giving a minimum estimated incidence in the UK of severe chemical corneal injury of 0.02 per 100,000. 66.7% of injuries were in males of working age, 50% occurred at work, and alkali was causative in 66.7%. Only one patient was wearing eye protection at the time of injury, 75% received immediate irrigation. Six patients required one or more surgical procedures, most commonly amniotic membrane graft. At 6 months' follow-up, the best-corrected visual acuity was 6/12 or better in five patients, and worse than 6/60 in two.

CONCLUSION: The incidence of severe chemical corneal injury in the UK is low. The cases that occur can require extended hospital treatment, with substantial ocular morbidity and visual sequelae. Current enforcement of eye protection in the workplace in the UK has probably contributed to a reduced incidence of severe ocular burns.

Home-based child development interventions for preschool children from socially disadvantaged families

BACKGROUND
Social disadvantage can have a significant impact on early child development, health and wellbeing. What happens during this critical period is important for all aspects of development. Caregiving competence and the quality of the environment play an important role in supporting development in young children and parents have an important role to play in optimising child development and mitigating the negative effects of social disadvantage. Home-based child development programmes aim to optimise children's developmental outcomes through educating, training and supporting parents in their own home to provide a more nurturing and stimulating environment for their child.

OBJECTIVES
To determine the effects of home-based programmes aimed specifically at improving developmental outcomes for preschool children from socially disadvantaged families.

SEARCH STRATEGY
We searched the following databases between 7 October and 12 October 2010: Cochrane Central Register of Controlled Trials (CENTRAL) (2010, Issue 4), MEDLINE (1950 to week 4, September 2010), EMBASE (1980 to Week 39, 2010), CINAHL (1937 to current), PsycINFO (1887 to current), ERIC (1966 to current), ASSIA (1987 to current), Sociological Abstracts (1952 to current), Social Science Citation Index (1970 to current). We also searched reference lists of articles.

SELECTION CRITERIA
Randomised controlled trials comparing home-based preschool child development interventions with a 'standard care' control. Participants were parents with children up to the age of school entry who were socially disadvantaged in respect of poverty, lone parenthood or ethnic minority status.

DATA COLLECTION AND ANALYSIS
Two authors independently selected studies, assessed the trials' risk of bias and extracted data.

RESULTS
We included seven studies, which involved 723 participants. We assessed four of the seven studies as being at high risk of bias and three had an unclear risk of bias; the quality of the evidence was difficult to assess as there was often insufficient detail reported to enable any conclusions to be drawn about the methodological rigour of the studies. Four trials involving 285 participants measured cognitive development and we synthesised these data in a meta-analysis. Compared to the control group, there was no statistically significant impact of the intervention on cognitive development (standardised mean difference (SMD) 0.30; 95% confidence interval -0.18 to 0.78). Only three studies reported socioemotional outcomes and there was insufficient data to combine into a meta-analysis. No study reported on adverse effects.

AUTHORS’ CONCLUSIONS
This review does not provide evidence of the effectiveness of home-based interventions that are specifically targeted at improving developmental outcomes for preschool children from socially disadvantaged families. Future studies should endeavour to better document and report their methodological processes.

GELIFICATION - A SIMPLE AND EFFICIENT METHOD FOR ON-CHIP STORAGE OF REAGENTS: TOWARDS LAB-ON-A-CHIP SYSTEMS FOR POINT-OF-CARE DIAGNOSTICS

In this study, we describe a simple and efficient method for on-chip storage of reagents for point-of-care (POC) diagnostics. The method is based on gelification of all reagents required for on-chip PCR-based diagnostics as a ready-to-use product. The result reported here is a key step towards the development of a ready and easy to use fully integrated Lab-on-a-chip (LOC) system for fast, cost-effective and efficient POC diagnostics analysis.

First steps: study protocol for a randomized controlled trial of the effectiveness of the Group Family Nurse Partnership (gFNP) program compared to routine care in improving outcomes for high-risk mothers and their children and preventing abuse

Background: Evidence from the USA suggests that the home-based Family Nurse Partnership program (FNP), extending from early pregnancy until infants are 24 months, can reduce the risk of child abuse and neglect throughout childhood. FNP is now widely available in the UK. A new variant, Group Family Nurse Partnership (gFNP) offers similar content but in a group context and for a shorter time, until infants are 12 months old. Each group comprises 8 to 12 women with similar expected delivery dates and their partners. Its implementation has been established but there is no evidence of its effectiveness.

Methods/Design: The study comprises a multi-site randomized controlled trial designed to identify the benefits of gFNP compared to standard care. Participants (not eligible for FNP) must be either aged <20 years at their last menstrual period (LMP) with one or more previous live births, or aged 20 to 24 at LMP with low educational qualifications and no previous live births. 'Low educational qualifications' is defined as not having both Maths and English Language GCSE at grade C or higher or, if they have both, no more than four in total at grade C or higher. Exclusions are: under 20 years and previously received home-based FNP and, in either age group, severe psychotic mental illness or not able to communicate in English. Consenting women are randomly allocated (minimized by site and maternal age group) when between 10 and 16 weeks pregnant to either to the 44 session gFNP program or to standard care after the collection of baseline information. Researchers are blind to group assignment. The primary outcomes at 12 months are child abuse potential based on the revised Adult-Adolescent Parenting Inventory and parent/infant interaction coded using the CARE Index based on a video-taped interaction. Secondary outcomes are maternal depression, parenting stress, health related quality of life, social support, and use of services.

Discussion: This is the first study of the effectiveness of gFNP in the UK. Results should inform decision-making about its delivery alongside universal services, potentially enabling a wider range of families to benefit from the FNP curriculum and approach to supporting parenting.