Centre-level variation in speech outcome and interventions, and factors associated with poor speech outcomes in 5-year-old children with non-syndromic unilateral cleft lip and palate:the Cleft Care UK study. Part 4

Objectives: To investigate centre-level variation in speech intervention and outcome and factors associated with a speech disorder in children in Cleft Care UK (CCUK). Setting and Sample Population: Two hundred and sixty-eight 5-year-old British children with non-syndromic unilateral cleft lip and palate recruited to CCUK. Materials and Methods: Centre-based therapists undertook audio-video recordings. Perceptual analysis was undertaken using the CAPS-A tool. Speech outcomes were based on structural and articulation scores, and intelligibility/distinctiveness. Between-centre variation in treatment and outcomes were examined using multilevel models. These models were extended to estimate the association between a range of factors (hearing loss, speech intervention, fistula, secondary speech surgery for velopharyngeal insufficiency, socio-economic status, gender, and parental happiness with speech) and speech outcomes. Results: There was centre-level variation in secondary speech surgery, speech intervention, structure and intelligibility outcomes. Children with a history of speech intervention had a lower odds of poor intelligibility/distinctiveness, 0.1 (95% CI: 0.0-0.4). Parental concern was associated with a higher odds of poor intelligibility/distinctiveness, 13.2 (95% CI: 4.9-35.1). Poor speech outcomes were associated with a fistula, secondary speech surgery and history of hearing loss. Conclusions: Within the centralized service there is centre-level variation in secondary speech surgery, intervention and speech outcomes. These findings support the importance of early management of fistulae, effective management of velopharyngeal insufficiency and hearing impairment, and most importantly speech intervention in the preschool years. Parental concern about speech is a good indicator of speech status

Disease trajectories, place and mode of death in people with head and neck cancer: findings from the ‘Head and Neck 5000’ population-based prospective clinical cohort study

Background: Few large studies describe initial disease trajectories and subsequent mortality in people with head and neck cancer. This is a necessary first step to identify the need for palliative care and associated services. Aim: To analyse data from the Head and Neck 5000 study to present mortality, place and mode of death within 12 months of diagnosis. Design: Prospective cohort study. Participants: In total, 5402 people with a new diagnosis of head and neck cancer were recruited from 76 cancer centres in the United Kingdom between April 2011 and December 2014. Results: Initially, 161/5402 (3%) and 5241/5402 (97%) of participants were treated with ‘non-curative’ and ‘curative’ intent respectively. Within 12 months, 109/161 (68%) in the ‘non-curative’ group died compared with 482/5241 (9%) in the ‘curative’ group. Catastrophic bleed was the terminal event for 10.4% and 9.8% of people in ‘non-curative’ and ‘curative’ groups respectively; terminal airway obstruction was recorded for 7.5% and 6.3% of people in the same corresponding groups. Similar proportions of people in both groups died in a hospice (22.9% ‘non-curative’; 23.5% ‘curative’) and 45.7% of the ‘curative’ group died in hospital. Conclusions: In addition to those with incurable head and neck cancer, there is a small but significant ‘curative’ subgroup of people who may have palliative needs shortly following diagnosis. Given the high mortality, risk of acute catastrophic event and frequent hospital death, clarifying the level and timing of palliative care services engagement would help provide assurance as to whether palliative care needs are being met

Centralization of cleft care in the UK. Part 6:a tale of two studies

OBJECTIVES: We summarize and critique the methodology and outcomes from a substantial study which has investigated the impact of reconfigured cleft care in the United Kingdom (UK) 15 years after the UK government started to implement the centralization of cleft care in response to an earlier survey in 1998, the Clinical Standards Advisory Group (CSAG). SETTING AND SAMPLE POPULATION: A UK multicentre cross-sectional study of 5-year-olds born with non-syndromic unilateral cleft lip and palate. Data were collected from children born in the UK with a unilateral cleft lip and palate between 1 April 2005 and 31 March 2007. MATERIALS AND METHODS: We discuss and contextualize the outcomes from speech recordings, hearing, photographs, models, oral health and psychosocial factors in the current study. We refer to the earlier survey and other relevant studies. RESULTS: We present arguments for centralization of cleft care in healthcare systems, and we evidence this with improvements seen over a period of 15 years in the UK. We also make recommendations on how future audit and research may configure. CONCLUSIONS: Outcomes for children with a unilateral cleft lip and palate have improved after the introduction of a centralized multidisciplinary service, and other countries may benefit from this model. Predictors of early outcomes are still needed, and repeated cross-sectional studies, larger longitudinal studies and adequately powered trials are required to create a research-led evidence-based (centralized) service

A cross-sectional survey of 5-year-old children with non-syndromic unilateral cleft lip and palate:the Cleft Care UK study. Part 1: background and methodology

OBJECTIVES: We describe the methodology for a major study investigating the impact of reconfigured cleft care in the United Kingdom (UK) 15 years after an initial survey, detailed in the Clinical Standards Advisory Group (CSAG) report in 1998, had informed government recommendations on centralization. SETTING AND SAMPLE POPULATION: This is a UK multicentre cross-sectional study of 5-year-olds born with non-syndromic unilateral cleft lip and palate. Children born between 1 April 2005 and 31 March 2007 were seen in cleft centre audit clinics. MATERIALS AND METHODS: Consent was obtained for the collection of routine clinical measures (speech recordings, hearing, photographs, models, oral health, psychosocial factors) and anthropometric measures (height, weight, head circumference). The methodology for each clinical measure followed those of the earlier survey as closely as possible. RESULTS: We identified 359 eligible children and recruited 268 (74.7%) to the study. Eleven separate records for each child were collected at the audit clinics. In total, 2666 (90.4%) were collected from a potential 2948 records. The response rates for the self-reported questionnaires, completed at home, were 52.6% for the Health and Lifestyle Questionnaire and 52.2% for the Satisfaction with Service Questionnaire. CONCLUSIONS: Response rates and measures were similar to those achieved in the previous survey. There are practical, administrative and methodological challenges in repeating cross-sectional surveys 15 years apart and producing comparable data

Coherent electron-phonon coupling and polaron-like transport in molecular wires

We present a technique to calculate the transport properties through one-dimensional models of molecular wires. The calculations include inelastic electron scattering due to electron-lattice interaction. The coupling between the electron and the lattice is crucial to determine the transport properties in one-dimensional systems subject to Peierls transition since it drives the transition itself. The electron-phonon coupling is treated as a quantum coherent process, in the sense that no random dephasing due to electron-phonon interactions is introduced in the scattering wave functions. We show that charge carrier injection, even in the tunneling regime, induces lattice distortions localized around the tunneling electron. The transport in the molecular wire is due to polaron-like propagation. We show typical examples of the lattice distortions induced by charge injection into the wire. In the tunneling regime, the electron transmission is strongly enhanced in comparison with the case of elastic scattering through the undistorted molecular wire. We also show that although lattice fluctuations modify the electron transmission through the wire, the modifications are qualitatively different from those obtained by the quantum electron-phonon inelastic scattering technique. Our results should hold in principle for other one-dimensional atomic-scale wires subject to Peierls transitions.Comment: 21 pages, 8 figures, accepted for publication in Phys. Rev. B (to appear march 2001

Density functional method for nonequilibrium electron transport

We describe an ab initio method for calculating the electronic structure, electronic transport, and forces acting on the atoms, for atomic scale systems connected to semi-infinite electrodes and with an applied voltage bias. Our method is based on the density functional theory (DFT) as implemented in the well tested Siesta approach (which uses non-local norm-conserving pseudopotentials to describe the effect of the core electrons, and linear combination of finite-range numerical atomic orbitals to describe the valence states). We fully deal with the atomistic structure of the whole system, treating both the contact and the electrodes on the same footing. The effect of the finite bias (including selfconsistency and the solution of the electrostatic problem) is taken into account using nonequilibrium Green's functions. We relate the nonequilibrium Green's function expressions to the more transparent scheme involving the scattering states. As an illustration, the method is applied to three systems where we are able to compare our results to earlier ab initio DFT calculations or experiments, and we point out differences between this method and existing schemes. The systems considered are: (1) single atom carbon wires connected to aluminum electrodes with extended or finite cross section, (2) single atom gold wires, and finally (3) large carbon nanotube systems with point defects.Comment: 18 pages, 23 figure

Common variants near MC4R are associated with fat mass, weight and risk of obesity.

To identify common variants influencing body mass index (BMI), we analyzed genome-wide association data from 16,876 individuals of European descent. After previously reported variants in FTO, the strongest association signal (rs17782313, P = 2.9 x 10(-6)) mapped 188 kb downstream of MC4R (melanocortin-4 receptor), mutations of which are the leading cause of monogenic severe childhood-onset obesity. We confirmed the BMI association in 60,352 adults (per-allele effect = 0.05 Z-score units; P = 2.8 x 10(-15)) and 5,988 children aged 7-11 (0.13 Z-score units; P = 1.5 x 10(-8)). In case-control analyses (n = 10,583), the odds for severe childhood obesity reached 1.30 (P = 8.0 x 10(-11)). Furthermore, we observed overtransmission of the risk allele to obese offspring in 660 families (P (pedigree disequilibrium test average; PDT-avg) = 2.4 x 10(-4)). The SNP location and patterns of phenotypic associations are consistent with effects mediated through altered MC4R function. Our findings establish that common variants near MC4R influence fat mass, weight and obesity risk at the population level and reinforce the need for large-scale data integration to identify variants influencing continuous biomedical traits

Physical activity attenuates the influence of FTO variants on obesity risk: A meta-analysis of 218,166 adults and 19,268 children

Background: The FTO gene harbors the strongest known susceptibility locus for obesity. While many individual studies have suggested that physical activity (PA) may attenuate the effect of FTO on obesity risk, other studies have not been able to confirm this interaction. To confirm or refute unambiguously whether PA attenuates the association of FTO with obesity risk, we meta-analyzed data from 45 studies of adults (n = 218,166) and nine studies of children and adolescents (n = 19,268). Methods and Findings: All studies identified to have data on the FTO rs9939609 variant (or any proxy [r2>0.8]) and PA were invited to participate, regardless of ethnicity or age of the participants. PA was standardized by categorizing it into a dichotomous variable (physically inactive versus active) in each study. Overall, 25% of adults and 13% of children were categorized as inactive. Interaction analyses were performed within each study by including the FTO×PA interaction term in an additive model, adjusting for age and sex. Subsequently, random effects meta-analysis was used to pool the interaction terms. In adults, the minor (A-) allele of rs9939609 increased the odds of obesity by 1.23-fold/allele (95% CI 1.20-1.26), but PA attenuated this effect (pinteraction= 0.001). More specifically, the minor allele of rs9939609 increased the odds of obesity less in the physically active group (odds ratio = 1.22/allele, 95% CI 1.19-1.25) than in the inactive group (odds ratio = 1.30/allele, 95% CI 1.24-1.36). No such interaction was found in children and adolescents. Concl