The use of eye-tracking technology as a tool to evaluate social cognition in people with an intellectual disability: a systematic review and meta-analysis.

BACKGROUND: Relatively little is known about social cognition in people with intellectual disability (ID), and how this may support understanding of co-occurring autism. A limitation of previous research is that traditional social-cognitive tasks place a demand on domain-general cognition and language abilities. These tasks are not suitable for people with ID and lack the sensitivity to detect subtle social-cognitive processes. In autism research, eye-tracking technology has offered an effective method of evaluating social cognition-indicating associations between visual social attention and autism characteristics. The present systematic review synthesised research which has used eye-tracking technology to study social cognition in ID. A meta-analysis was used to explore whether visual attention on socially salient regions (SSRs) of stimuli during these tasks correlated with degree of autism characteristics presented on clinical assessment tools. METHOD: Searches were conducted using four databases, research mailing lists, and citation tracking. Following in-depth screening and exclusion of studies with low methodological quality, 49 articles were included in the review. A correlational meta-analysis was run on Pearson's r values obtained from twelve studies, reporting the relationship between visual attention on SSRs and autism characteristics. RESULTS AND CONCLUSIONS: Eye-tracking technology was used to measure different social-cognitive abilities across a range of syndromic and non-syndromic ID groups. Restricted scan paths and eye-region avoidance appeared to impact people's ability to make explicit inferences about mental states and social cues. Readiness to attend to social stimuli also varied depending on social content and degree of familiarity. A meta-analysis using a random effects model revealed a significant negative correlation (r = -.28, [95% CI -.47, -.08]) between visual attention on SSRs and autism characteristics across ID groups. Together, these findings highlight how eye-tracking can be used as an accessible tool to measure more subtle social-cognitive processes, which appear to reflect variability in observable behaviour. Further research is needed to be able to explore additional covariates (e.g. ID severity, ADHD, anxiety) which may be related to visual attention on SSRs, to different degrees within syndromic and non-syndromic ID groups, in order to determine the specificity of the association with autism characteristics.

Prepared for practice? a national survey of UK foundation doctors and their supervisors.

BACKGROUND: Mandatory induction for foundation year 1 trainees (F1s) was introduced in 2012 to ease the transition from student to doctor. The aims of this national study were to assess anxiety levels and preparedness in the 2012 F1 cohort and whether these varied according to medical school of graduation and foundation school of practice. METHODS: Online surveys were completed anonymously and voluntarily by F1s and F1 supervisors from participating foundation schools. Questions assessed how prepared F1s were for practice and how well they coped with the transition from medical school. A validated screening tool was used to assess anxiety levels. RESULTS: 1829 F1s and 1145 supervisors participated. 27.8% of F1s screened positive for pathological anxiety. Increased time spent in a 'shadowing' type role during medical school and each additional day of induction reduced anxiety levels. How prepared F1s were for different aspects of their jobs varied according to medical and foundation school, from both the F1 and supervisor perspective. CONCLUSIONS: How prepared F1s feel can vary according to the medical school of graduation and foundation school of practice. F1 anxiety may be reduced with a prolonged F1 induction programme and an extended shadowing period during the final year of medical school.

Radial flow permeability testing of an argillaceous limestone.

Argillaceous Lindsay limestone is the geologic storage formation that will be encountered at the site for the construction of a deep ground repository in Ontario, Canada, for the storage of low to intermediate level nuclear waste. The permeability of the Lindsay limestone is a key parameter that will influence the long-term movement of radionuclides from the repository to the geosphere. This paper describes the use of both steady-state and transient radial flow laboratory tests to determine the permeability of this argillaceous limestone. The interpretation of the tests is carried out using both analytical results and computational models of flow problems that exhibit radial symmetry. The results obtained from this research investigation are compared with the data available in the literature for similar argillaceous limestones mainly found in the Lindsay (Cobourg) formation. The experiments give permeabilities in the range of 1.0 × 10(-22) to 1.68 × 10(-19) m(2) for radial flows that are oriented along bedding planes under zero axial stress. The factors influencing transient pulse tests in particular and the interpretation of the results are discussed.

Referral proformas improve compliance to national colorectal 2-week wait targets: does this affect cancer detection rates?

AIM: To facilitate implementation of National Institute for Health and Clinical Excellence (NICE) guidelines for urgent colorectal cancer referral, local cancer networks have promoted the use of standardized proformas in primary care. This clinical audit assessed use of the proforma within the Thames Valley Cancer Network (TVCN) to see whether increased proforma use was associated with higher compliance to NICE guidelines and higher cancer detection rates. METHOD: All 2-week wait referrals for lower bowel cancer to the six Acute NHS Trusts in the TVCN received during the month of June 2010 were identified, anonymized and analysed in relation to colorectal cancer detection rates. RESULTS: Of the 586 referrals audited, proforma usage varied significantly across the six Acute NHS Trusts from 18% to 96%. Referral letters from primary care had NICE compliance ranging from 30 to 50%. In those which received a referral protocol, 50-90% were NICE compliant. Proforma use was associated with higher cancer detection rates (P = 0.03). CONCLUSION: These results have wide-ranging implications since they suggest that the adoption of a simple proforma in primary care can improve the effectiveness of referral for suspected cancer.

Isolation and crystallization of a chimeric Qß replicase containing Thermus thermophilus EF-Ts.

Qß replicase is a protein complex responsible for the replication of the genomic RNA of bacteriophage Qß. In addition to the phage-encoded catalytic ß subunit, it recruits three proteins from the host Escherichia coli cell: elongation factors EF-Tu and EF-Ts and ribosomal protein S1. We prepared a chimeric Qß replicase in which the E. coli EF-Ts is replaced with EF-Ts from Thermus thermophilus. The chimeric protein is produced in E. coli cells during coexpression of the genes encoding the ß subunit and thermophilic EF-Ts. The developed isolation procedure yields a substantially homogeneous preparation of the chimeric replicase. Unlike the wild-type enzyme, the S1-less chimeric replicase could be crystallized. This result facilitates studies on the structure of Qß replicase and the mechanism of recognition of its templates that can replicate in vitro at a record rate.

A structural view of translation initiation in bacteria.

The assembly of the protein synthesis machinery occurs during translation initiation. In bacteria, this process involves the binding of messenger RNA(mRNA) start site and fMet-tRNA(fMet) to the ribosome, which results in the formation of the first codon-anticodon interaction and sets the reading frame for the decoding of the mRNA. This interaction takes place in the peptidyl site of the 30S ribosomal subunit and is controlled by the initiation factors IF1, IF2 and IF3 to form the 30S initiation complex. The binding of the 50S subunit and the ejection of the IFs mark the irreversible transition to the elongation phase. Visualization of these ligands on the ribosome has been achieved by cryo-electron microscopy and X-ray crystallography studies, which has helped to understand the mechanism of translation initiation at the molecular level. Conformational changes associated with different functional states provide a dynamic view of the initiation process and of its regulation.

[Messenger RNA movement on the ribosome].

Recent X-ray and cryo-EM studies of 70S ribosome complexes containing different types of messenger RNAs (mRNA) and transfer RNA (tRNA) have been reviewed. Changes of the mRNA path on the ribosome at initiation and elongation states have been described. Authors suggested, that the specific region of ribosomal 30S subunit ("platform") is a ribosome binding site of regulatory domains of mRNA which locates on the non-translated 5'-end of the mRNA.

Contrasting views and experiences of health professionals on the management of comorbid substance misuse and mental disorders.

OBJECTIVES: To determine opinions and experiences of health professionals concerning the management of people with comorbid substance misuse and mental health disorders. METHOD: We conducted a survey of staff from mental health services and alcohol and drug services across Queensland. Survey items on problems and potential solutions had been generated by focus groups. RESULTS: We analysed responses from 112 staff of alcohol and drug services and 380 mental health staff, representing a return of 79% and 42% respectively of the distributed surveys. One or more issues presented a substantial clinical management problem for 98% of respondents. Needs for increased facilities or services for dual disorder clients figured prominently. These included accommodation or respite care, work and rehabilitation programs, and support groups and resource materials for families. Needs for adolescent dual diagnosis services and after-hours alcohol and drug consultations were also reported. Each of these issues raised substantial problems for over 70% of staff. Another set of problems involved coordination of client care across mental health and alcohol and drug services, including disputes over duty of care. Difficulties with intersectoral liaison were more pronounced for alcohol and drug staff than for mental health. A majority of survey respondents identified 13 solutions as practical. These included routine screening for dual diagnosis at intake, and a range of proposals for closer intersectoral communication such as exchanging client information, developing shared treatment plans, conducting joint case conferences and offering consultation facilities. CONCLUSIONS: A wide range of problems for the management of comorbid disorders were identified. While solution of some problems will require resource allocation, many may be addressed by closer liaison between existing services.

Induction of ovulation in women undergoing assisted reproductive techniques: recombinant human FSH (follitropin alpha) versus highly purified urinary FSH (urofollitropin HP).

This multicentre, open, randomized, study compared the efficacy and safety of recombinant follicle stimulating hormone (rFSH; follitropin alpha) with highly purified urinary human FSH (uFSH; urofollitropin HP) in women undergoing ovulation induction for assisted reproductive techniques. Following long down-regulation with buserelin, patients received two ampoules of 75 IU (150 IU) s.c. rFSH or highly purified uFSH for 6 days, after which the dose could be increased until they fulfilled the criteria for human chorionic gonadotrophin (HCG) administration. Of 168 patients recruited, 155 received at least one dose of FSH, and 137 received HCG [68: rFSH (85%); 69: uFSH (92%)]. Following oocyte retrieval and fertilization, up to three embryos were replaced/patient and luteal support was given. The mean number of oocytes retrieved/patient was 10.2 +/- 6.0 for rFSH patients compared with 10.8 +/- 6.1 in the uFSH group (not significant). There was a trend towards fewer ampoules used (22.3 +/- 6.5 versus 24.3 +/- 6.5), higher pregnancy (44.3 versus 41.4%) and live birth rates (33.8 versus 26.7%), as well as a lower miscarriage rate (0.0 versus 16.7%) in favour of rFSH. However, no significant differences in efficacy parameters were recorded. Ovarian hyperstimulation syndrome occurred in 8.6% and 7.9% of rFSH and uFSH patients respectively. In conclusion, this protocol was effective in inducing multiple follicular development and high numbers of oocytes were retrieved with both drugs.

A survey of contact with offspring and assistance with child care among parents with psychotic disorders.

To help improve services for parents with psychotic disorders, patients with such disorders in three treatment agencies in Queensland, Australia, were surveyed about whether they were parents, how much contact they had with their offspring, and who provided assistance with child care. Of the 342 individuals with psychotic disorders who participated in the study, 124 were parents. Forty-eight parents in the study had children under age 16, and 20 of these parents (42 percent) had their children living with them. Most parents relied on relatives or friends for assistance with child care. Barriers to child care services identified by parents were inability to pay, lack of local services, and fear of losing custody of children.

The fertility and fecundity of patients with psychoses.

OBJECTIVE: Previous research has suggested that patients with schizophrenia have fewer offspring compared to the general population. Reduced fertility in a disorder with a strong genetic component and an apparently stable incidence has implications for models of genetic transmission. There is also a need to obtain contemporary estimates of the prevalence of parenthood among subjects with psychotic disorders in order to inform service planning. The aim of this study was to determine the fertility and fecundity of a representative sample of individuals with psychoses who were in contact with mental health services, and to explore the interactions between age at first diagnosis and fertility. METHOD: All clients of two community mental health clinics and an extended-care psychiatric hospital were surveyed. Data on diagnosis, age at first diagnosis, and the number and age of offspring were collected. Based on interviews with the proband and chart review, a genogram of the probands' family was drawn that identified sex, age, affected status and the number of offspring for each patient and their siblings. RESULTS: In total, 36% of all patients were parents. Most women with psychoses (59%) were mothers. Patients with psychoses had fewer offspring compared to their unaffected same-sex siblings. This was especially the case for men with non-affective psychoses. Higher levels of fertility were associated with a later age at first diagnosis. CONCLUSION: The consistent finding of reduced 'reproductive fitness' in those with non-affective psychoses needs to be incorporated in the genetic epidemiology of these disorders. Despite this reduction in fertility and fecundity, many patients with psychoses are parents. Services need to remain mindful of the special needs of these patients.

Mutations in CUBN, encoding the intrinsic factor-vitamin B12 receptor, cubilin, cause hereditary megaloblastic anaemia 1.

Megaloblastic anaemia 1 (MGA1, OMIM 261100) is a rare, autosomal recessive disorder characterized by juvenile megaloblastic anaemia, as well as neurological symptoms that may be the only manifestations. At the cellular level, MGA1 is characterized by selective intestinal vitamin B12 (B12, cobalamin) malabsorption. MGA1 occurs worldwide, but its prevalence is higher in several Middle Eastern countries and Norway, and highest in Finland (0.8/100,000). We previously mapped the MGA1 locus by linkage analysis in Finnish and Norwegian families to a 6-cM region on chromosome 10p12.1 (ref. 8). A functional candidate gene encoding the intrinsic factor (IF)-B12 receptor, cubilin, was recently cloned; the human homologue, CUBN, was mapped to the same region. We have now refined the MGA1 region by linkage disequilibrium (LD) mapping, fine-mapped CUBN and identified two independent disease-specific CUBN mutations in 17 Finnish MGA1 families. Our genetic and molecular data indicate that mutations in CUBN cause MGA1.

Crystallization of human complement component C5.

Human complement component C5 has been crystallized using a low-salt batch technique. The crystals are large hexagonal bi-pyramids often larger than 1.5 mm. Although these crystals were grown in low salt (0.1 M NaCl), they are remarkably stable for at least 2 months at 281 K and they are not dissolved in aqueous buffers containing up to 2 M sodium chloride. The space group is P3121 or P3221, and the cell parameters were determined to be a = 144.9, b = 144.9, c = 243.1 A; alpha = 90 degrees, beta = 90, gamma = 120 degrees. At room temperature and cryo-temperatures the crystals diffract at best to 6 A using rotating-anode X-ray sources. Using synchrotron radiation with cryoprotection using 40%(v/v) PEG 400 the resolution limit can be extended to 3.3 A. In both cases the crystals show significant anisotropy, with relatively weaker reflections at higher resolution in the a*b* plane.

The relationship between follicular fluid aspirate volume and oocyte maturity in in-vitro fertilization cycles.

As a consequence of multiple follicular growth during ovarian stimulation for in-vitro fertilization (IVF), follicles of varying sizes often yield oocytes that vary in maturity and morphology of the oocyte-cumulus-corona complex. The objective of this prospective study was to explore the relationship between follicular fluid aspirate volume and the oocyte's developmental potential in an IVF treatment cycle. In total 9933 follicles were studied from 400 patients who underwent 535 consecutive IVF treatment cycles at St James's University Hospital, Leeds, UK, between February 1995 and February 1996. The volume of each individual follicle aspirated was recorded and related to the probability of obtaining an oocyte, its fertilizing capacity, the cleavage rate and the quality of embryos derived. We found no statistically significant difference in oocyte recovery rates between follicles with an aspirate volume < or = 1 ml and follicles with a volume > 1 ml. Although oocytes obtained from follicles with an aspirate volume > or = 1 ml showed a significantly lower fertilization rate, they went on to cleave at the same rate as oocytes obtained from larger follicles and resulted in embryos of comparable quality. Furthermore, there was no statistically significant difference in the implantation, clinical pregnancy or live birth rates per cycle between embryos derived from follicles with an aspirate volume < or = 1 ml and those derived from follicles with an aspirate volume > 1 ml. We conclude that follicular size and the oocyte's developmental potential in the stimulated ovary are not closely related and can be independent. This is in contrast to the Graafian follicle and the pre-ovulatory oocyte in the natural cycle.

Crystal structure of the receptor-binding domain of alpha 2-macroglobulin.

BACKGROUND: The large plasma proteinase inhibitors of the alpha 2-macroglobulin superfamily inhibit proteinases by capturing them within a central cavity of the inhibitor molecule. After reaction with the proteinase, the alpha-macroglobulin-proteinase complex binds to the alpha-macroglobulin receptor, present in the liver and other tissues, and becomes endocytosed and rapidly removed from the circulation. The complex binds to the receptor via recognition sites located on a separate domain of approximately 138 residues positioned at the C terminus of the alpha-macroglobulin subunit. RESULTS: The crystal structure of the receptor-binding domain of bovine alpha 2-macroglobulin (bRBD) has been determined at a resolution of 1.9 A. The domain primarily comprises a nine-strand beta structure with a jelly-roll topology, but also contains two small alpha helices. CONCLUSIONS: The surface patch responsible for receptor recognition is thought to involve residues located on one of the two alpha helices of the bRBD as well as residues in two of the beta strands. Located on this alpha helix are two lysine residues that are important for receptor binding. The structure of bRBD is very similar to the approximately 100-residue C-terminal domain of factor XIII, a transglutaminase from the blood coagulation system.

Noncytopathogenic bovine viral diarrhea virus (BVDV) reduces cleavage but increases blastocyst yield of in vitro produced embryos.

The growing application of in vitro embryo production systems that utilize slaughterhouse tissues of animals of unknown health status conveys the risk of disease transmission. One pathogen of concern in this regard is bovine viral diarrhea virus (BVDV), and the objective of this study was to investigate the effect of BVDV on in vitro embryonic development. A bovine in vitro embryo production system was experimentally infected with BVDV at 2 stages: prior to in vitro maturation by incubating cumulus-oocyte complexes (COC) with virus (strain Pe515; titer 10(6.2) tissue culture infective dose (TCID)50/mL) or vehicle for 2 h, and then during in vitro culture by the use of BVDV infected granulosa cells. Exposure to BVDV throughout in vitro production reduced cleavage rates (P = 0.01) but increased (P = 0.05) the number of embryos that reached the 8-cell stage when expressed as a percentage of cleaved oocytes. Blastocyst yield was increased by the presence of virus when expressed as a proportion of oocytes (P = 0.0034) or of those cleaved (P < 0.0001). The percentage of total blastocyst yield on Days 7, 8 and 9 for the control and virus treatments was 20, 51, 29 and 29, 41, and 29%, respectively, indicating that the rate of blastocyst development was nonsignificantly faster in the virus-treated group (P = 0.06). These results indicate that the presence of non-cytopathogenic BVDV in an in vitro production system may reduce cleavage rates but allow those cleaved to develop to blastocysts at a higher rate.

Communication skill and behaviour disorder.

The aim was to identify changes in communication skills and behaviour disorder of 15 clients with learning difficulties 6 mo. and 1 yr. after they moved from large- to small-scale accommodations. Clients were allocated into a group of 6 with profound multiple learning difficulties, a preverbal group of 5, and a verbal group of 4. Communication skills were measured using the Preverbal Communication Schedule, and behavioural disorder was measured using the Aberrant Behaviour Checklist. Analysis showed that from the baseline to one year follow-up, there was a significant increase from baseline in social withdrawal by the clients with multiple difficulties but that there were improvements in communication skills of both preverbal and verbal clients. No control group was involved.

Crystallisation and preliminary X-ray analysis of the receptor-binding domain of human and bovine alpha 2-macroglobulin.

The receptor-binding domains (RBDs) of human and bovine alpha 2-macroglobulin (alpha 2M) have been isolated after limited proteolysis of methylamine-treated alpha 2M with papain. Single crystals of the RBDs have been grown by vapour diffusion. Crystals of human RBD are very thin plates unsuited for data collection. However, crystals of RBD from bovine alpha 2M give diffraction patterns suitable for X-ray analysis, and a complete dataset with a maximum resolution of 2.3 A has been collected with synchrotron radiation at cryogenic temperature. The crystals belong to spacegroup P3(1)21 or P3(2)21 with cell parameters a = b = 106.8 A, c = 72.2 A.

A rapid method for mRNA detection in single-cell biopsies from preimplantation-stage bovine embryos.

Major questions concerning the control of development and gene expression at the cellular level are still unanswered. Nowhere is this more evident than during the earliest stages of development and embryogenesis. This study describes the detection of specific gene transcripts in single cells derived from bovine embryos. Following in vitro fertilization (IVF) and in vitro culture (IVC) of bovine embryos, small groups of cells and even single blastomeres from 32 to 64-cell embryos were micromanipulated into individual tubes for analysis of cytoplasmic RNAs. Reverse transcriptase-PCR was applied to cell lysates for the amplification of beta-actin mRNA transcripts. Primers were designed to flank an intron expected to be present within genomic DNA sequences, thus allowing for simple differentiation between DNA- and RNA-derived amplification products. Using a 50-cycle amplification profile, a 260 bp band could be seen as a PCR product derived from a single blastomere following electrophoresis in an ethidium bromide-stained agarose gel. The identity of the band was verified by DNA sequence determination and diagnostic restriction digestion. Lysates derived from single blastomeres in this way have been used for simultaneously phenotyping multiple RNA products. This capability allows the spatial analysis of gene expression and development within embryos from the earliest stages of cellular differentiation.