The effect of cleft lip on socio-emotional functioning in school-aged children

Background: Children with cleft lip are known to be at raised risk for socio-emotional difficulties, but the nature of these problems and their causes are incompletely understood; longitudinal studies are required that include comprehensive assessment of child functioning, and consideration of developmental mechanisms. Method: Children with cleft lip (with and without cleft palate) (N = 93) and controls (N = 77), previously studied through infancy, were followed up at 7 years, and their socio-emotional functioning assessed using teacher and maternal reports, observations of social interactions, and child social representations (doll play). Direct and moderating effects of infant attachment and current parenting were investigated, as was the role of child communication difficulties and attractiveness. Results: Children with clefts had raised rates of teacher-reported social problems, and anxious and withdrawn-depressed behaviour; direct observations and child representations also revealed difficulties in social relationships. Child communication problems largely accounted for these effects, especially in children with cleft palate as well as cleft lip. Insecure attachment contributed to risk in both index and control groups, and a poorer current parenting environment exacerbated the difficulties of those with clefts. Conclusions: Children with clefts are at raised risk for socio-emotional difficulties in the school years; clinical interventions should focus on communication problems and supporting parenting; specific interventions around the transition to school may be required. More generally, the findings reflect the importance of communication skills for children’s peer relations.

Quantifying the response of the ORAC aerosol optical depth retrieval for MSG SEVIRI to aerosol model assumptions

We test the response of the Oxford-RAL Aerosol and Cloud (ORAC) retrieval algorithm for MSG SEVIRI to changes in the aerosol properties used in the dust aerosol model, using data from the Dust Outflow and Deposition to the Ocean (DODO) flight campaign in August 2006. We find that using the observed DODO free tropospheric aerosol size distribution and refractive index increases simulated top of the atmosphere radiance at 0.55 µm assuming a fixed erosol optical depth of 0.5 by 10–15 %, reaching a maximum difference at low solar zenith angles. We test the sensitivity of the retrieval to the vertical distribution f the aerosol and find that this is unimportant in determining simulated radiance at 0.55 µm. We also test the ability of the ORAC retrieval when used to produce the GlobAerosol dataset to correctly identify continental aerosol outflow from the African continent and we find that it poorly constrains aerosol speciation. We develop spatially and temporally resolved prior distributions of aerosols to inform the retrieval which incorporates five aerosol models: desert dust, maritime, biomass burning, urban and continental. We use a Saharan Dust Index and the GEOS-Chem chemistry transport model to describe dust and biomass burning aerosol outflow, and compare AOD using our speciation against the GlobAerosol retrieval during January and July 2006. We find AOD discrepancies of 0.2–1 over regions of intense biomass burning outflow, where AOD from our aerosol speciation and GlobAerosol speciation can differ by as much as 50 - 70 %.

State estimation using model order reduction for unstable systems

The problem of state estimation occurs in many applications of fluid flow. For example, to produce a reliable weather forecast it is essential to find the best possible estimate of the true state of the atmosphere. To find this best estimate a nonlinear least squares problem has to be solved subject to dynamical system constraints. Usually this is solved iteratively by an approximate Gauss–Newton method where the underlying discrete linear system is in general unstable. In this paper we propose a new method for deriving low order approximations to the problem based on a recently developed model reduction method for unstable systems. To illustrate the theoretical results, numerical experiments are performed using a two-dimensional Eady model – a simple model of baroclinic instability, which is the dominant mechanism for the growth of storms at mid-latitudes. It is a suitable test model to show the benefit that may be obtained by using model reduction techniques to approximate unstable systems within the state estimation problem.

Effects of omega-3 fatty acids on immune function in broiler chickens

There is interest in the enrichment of poultry meat with long-chain n-3 polyunsaturated fatty acids in order to increase the consumption of these fatty acids by humans. However, there is concern that high levels of n-3 polyunsaturated fatty acids may have detrimental effects on immune function in chickens. The effect of feeding increasing levels of fish oil (FO) on immune function was investigated in broiler chickens. Three-week-old broilers were fed 1 of 4 wheat-soybean basal diets that contained 0, 30, 50, or 60 g/kg of FO until slaughter. At slaughter, samples of blood, bursa of Fabricius, spleen, and thymus were collected from each bird. A range of immune parameters, including immune tissue weight, immuno-phenotyping, phagocytosis, and cell proliferation, were assessed. The pattern of fatty acid incorporation reflected the fatty acid composition of the diet. The FO did not affect the weight of the spleen, but it did increase thymus weight when fed at 50 g/kg (P < 0.001). Fish oil also lowered bursal weights when fed at 50 or 60 g/kg (P < 0.001). There was no significant effect of FO on immune cell phenotypes in the spleen, thymus, bursa, or blood. Feeding 60 g/kg of FO significantly decreased the percentage of monocytes engaged in phagocytosis, but it increased their mean fluorescence intensity relative to that of broilers fed 50 g/kg of FO. Lymphocyte proliferation was significantly decreased after feeding broiler chickens diets rich in FO when expressed as division index or proliferation index, although there was no significant effect of FO on the percentage of divided cells. In conclusion, dietary n-3 polyunsaturated fatty acids decrease phagocytosis and lymphocyte proliferation in broiler chickens, highlighting the need for the poultry industry to consider the health status of poultry when poultry meat is being enriched with FO.

Eight-plex iTRAQ analysis of variant metastatic human prostate cancer cells identifies candidate biomarkers of progression: an exploratory study.

BACKGROUND: Due to the heterogeneity in the biological behavior of prostate cancer, biomarkers that can reliably distinguish indolent from aggressive disease are urgently needed to inform treatment choices. METHODS: We employed 8-plex isobaric Tags for Relative and Absolute Quantitation (iTRAQ), to profile the proteomes of two distinct panels of isogenic prostate cancer cells with varying growth and metastatic potentials, in order to identify novel biomarkers associated with progression. The LNCaP, LNCaP-Pro5, and LNCaP-LN3 panel of cells represent a model of androgen-responsive prostate cancer, while the PC-3, PC-3M, and PC-3M-LN4 panel represent a model of androgen-insensitive disease. RESULTS: Of the 245 unique proteins identified and quantified (>or=95% confidence; >or=2 peptides/protein), 17 showed significant differential expression (>or=+/-1.5), in at least one of the variant LNCaP cells relative to parental cells. Similarly, comparisons within the PC-3 panel identified 45 proteins to show significant differential expression in at least one of the variant PC-3 cells compared with parental cells. Differential expression of selected candidates was verified by Western blotting or immunocytochemistry, and corresponding mRNA expression was determined by quantitative real-time PCR (qRT-PCR). Immunostaining of prostate tissue microarrays for ERp5, one of the candidates identified, showed a significant higher immunoexpression in pre-malignant lesions compared with non-malignant epithelium (P < 0.0001, Mann-Whitney U-test), and in high Gleason grade (4-5) versus low grade (2-3) cancers (P < 0.05). CONCLUSIONS: Our study provides proof of principle for the application of an 8-plex iTRAQ approach to uncover clinically relevant candidate biomarkers for prostate cancer progression.

A pharmacist-led information technology intervention for medication errors (PINCER): a multicentre, cluster randomised, controlled trial and cost-effectiveness analysis

Background: Medication errors are common in primary care and are associated with considerable risk of patient harm. We tested whether a pharmacist-led, information technology-based intervention was more effective than simple feedback in reducing the number of patients at risk of measures related to hazardous prescribing and inadequate blood-test monitoring of medicines 6 months after the intervention. Methods: In this pragmatic, cluster randomised trial general practices in the UK were stratified by research site and list size, and randomly assigned by a web-based randomisation service in block sizes of two or four to one of two groups. The practices were allocated to either computer-generated simple feedback for at-risk patients (control) or a pharmacist-led information technology intervention (PINCER), composed of feedback, educational outreach, and dedicated support. The allocation was masked to general practices, patients, pharmacists, researchers, and statisticians. Primary outcomes were the proportions of patients at 6 months after the intervention who had had any of three clinically important errors: non-selective non-steroidal anti-inflammatory drugs (NSAIDs) prescribed to those with a history of peptic ulcer without co-prescription of a proton-pump inhibitor; β blockers prescribed to those with a history of asthma; long-term prescription of angiotensin converting enzyme (ACE) inhibitor or loop diuretics to those 75 years or older without assessment of urea and electrolytes in the preceding 15 months. The cost per error avoided was estimated by incremental cost-eff ectiveness analysis. This study is registered with Controlled-Trials.com, number ISRCTN21785299. Findings: 72 general practices with a combined list size of 480 942 patients were randomised. At 6 months’ follow-up, patients in the PINCER group were significantly less likely to have been prescribed a non-selective NSAID if they had a history of peptic ulcer without gastroprotection (OR 0∙58, 95% CI 0∙38–0∙89); a β blocker if they had asthma (0∙73, 0∙58–0∙91); or an ACE inhibitor or loop diuretic without appropriate monitoring (0∙51, 0∙34–0∙78). PINCER has a 95% probability of being cost eff ective if the decision-maker’s ceiling willingness to pay reaches £75 per error avoided at 6 months. Interpretation: The PINCER intervention is an effective method for reducing a range of medication errors in general practices with computerised clinical records. Funding: Patient Safety Research Portfolio, Department of Health, England.