Online Resources for Robin Sequence; an Analysis of Readability.

The objective was to evaluate the readability of easily accessible parent-directed information concerning Robin Sequence (RS) online, compared to the American Medical Association (AMA)-recommended sixth grade (age 11-12) readability level.A Google search of the term "Pierre Robin Sequence information" was performed. The first ten websites were evaluated using six commonly used readability formulas. Sample texts from three websites were 'translated' by the authors, with the aim of achieving a sixth grade readability level.The following outcomes were used: Automated Readability Index (ARI), Coleman Liau Index (CLI), Gunning Fog Score, Simple Measure of Gobbledygook (SMOG), Flesch Kincaid Grade Level (FKGL), and Flesch Reading Ease (FRE) score.The mean pooled grade level of the top 10 included websites was 12.1 (age 17-18). The overall FRE Index was 45.8, which is equivalent to a College-grade reading level. The mean grade level by each test used was: Flesch-Kincaid Grade Level 11.6 (age 16-17), Gunning Fog Score 13.3 (age 18+), SMOG 10.0 (age 14-15), Coleman-Liau Index 13.8 (age 18+), and ARI 12.0 (age 17-18). The author-translated resources achieved pooled mean grade levels of 6.3-6.5.Parent-directed online materials concerning RS have a readability in excess of the AMA-recommended sixth grade reading level. Even though the condition is complex, more readable resources are achievable. Coproduction of parent-directed resources in association with public an patient involvement (PPI) contributors is encouraged.

Pregnancy rates and outcomes in women with cystic fibrosis in the UK: comparisons with the general population before and after the introduction of disease-modifying treatment, 2003-17.

OBJECTIVE: To compare pregnancy rates and outcomes for women with cystic fibrosis in the UK with those of the general population and assess the effect of the introduction of disease-modifying treatment. DESIGN: A population-based longitudinal study, 2003-17. SETTING: United Kingdom. POPULATION: Women aged 15-44 years in the UK cystic fibrosis (CF) Registry compared with women in England and Wales. METHODS: We calculated pregnancy and live-birth rates for the CF population and the general population of England and Wales. For women with CF we compared pregnancy rates before and after ivacaftor was introduced in 2013. We further used CF registry data to assess pregnancy outcomes for mothers with CF, and to assess the relationship between maternal pre-pregnancy lung function and nutritional status and child gestational age. MAIN OUTCOME MEASURES: Pregnancy and live-birth rates and child gestational age. RESULTS: Of 3831 women with CF, 661 reported 818 pregnancies. Compared with the general population, the pregnancy rate was 3.3 times lower in the CF population (23.5 versus 77.7 per 1000 woman-years); the live-birth rate was 3.5 times lower (17.4 versus 61.4 per 1000 woman-years) with 70% of pregnancies in CF women resulting in live births; termination of pregnancy rates were also lower (9% versus 22%). Pregnancy rates increased post-ivacaftor for eligible women with CF, from 29.7 to 45.7 per 1000 woman-years. There was no association between pre-pregnancy lung function/nutrition status and gestational age. CONCLUSIONS: Pregnancy rates in women with CF are about one-third of the rates in the general population with favourable outcomes, and increased for eligible women post-ivacaftor. TWEETABLE ABSTRACT: Pregnancy rates in women with CF are about a third of the rate in England and Wales with 70% live births. Ivacaftor increases the rate.

Initiating home spirometry for children during the COVID-19 pandemic - A practical guide.

The COVID-19 pandemic has led to a rapid escalation in use of home monitoring and video consultations in children with a variety of chronic respiratory conditions. Our department set up a home spirometry service from scratch once it became evident that we needed to keep patients away from hospital clinics whenever possible. We faced a number of challenges but now have around 400 children using home spirometers. There are a number of portable spirometers available, some with online platforms. The technology, particularly the software/apps interface, has been improved by the companies in response to issues that have arisen. We believe the use of home monitoring is here to stay.

Communicating cystic fibrosis newborn screening results to parents.

The way results of cystic fibrosis (CF) newborn screening are communicated to parents is critical yet is done differently across the globe. We surveyed parents of 101 children in our tertiary London paediatric centre with a 48% response rate. Parental responses were as follows: 40/42 (95%) said the information could not have been given over the phone and 39/43 (91%) said they wanted both partners present; 27/42 (64%) said it was helpful having the health visitor also present; and 37/40 (92%) felt it was acceptable to wait until the next day for the sweat test. We have reduced the time from first contact to arriving in the home to 2-3 h.Conclusion: We believe that this survey backs up our approach of a home visit by a CF nurse specialist with the family's health visitor to break the news. This is challenging in the current COVID-19 pandemic. What is Known: • Breaking bad news can have a lasting impact on parents when not done the right way. • Giving results of cystic fibrosis (CF) newborn screening is done differently within the UK and around the world. What is New: • Our parental survey revealed that the majority (92%) believed this should be done face to face and not over the telephone. • There was a mixed response to whether the parents should be told the genotype (assuming the CF centre knew), and thus the CF diagnosis before the confirmatory sweat test was carried out.

Restoration of exocrine pancreatic function in older children with cystic fibrosis on ivacaftor.

Prior to the use of cystic fibrosis (CF) modulator therapy, exocrine pancreatic insufficiency in CF was thought to be irreversible. Improvement in pancreatic function on ivacaftor has been reported in open label studies in 1-5 year olds. The mechanism by which ivacaftor might improve exocrine pancreatic function is unclear. Although the effect of ivacaftor on pancreatic function may be more significant in younger children, evidence is mounting that there may still be potential for improvement in older children on long term therapy.

Primary Ciliary Dyskinesia Due to Microtubular Defects is Associated with Worse Lung Clearance Index.

PURPOSE: Primary ciliary dyskinesia (PCD) is characterised by repeated upper and lower respiratory tract infections, neutrophilic airway inflammation and obstructive airway disease. Different ultrastructural ciliary defects may affect lung function decline to different degrees. Lung clearance index (LCI) is a marker of ventilation inhomogeneity that is raised in some but not all patients with PCD. We hypothesised that PCD patients with microtubular defects would have worse (higher) LCI than other PCD patients. METHODS: Spirometry and LCI were measured in 69 stable patients with PCD. Age at testing, age at diagnosis, ethnicity, ciliary ultrastructure, genetic screening result and any growth of Pseudomonas aeruginosa was recorded. RESULTS: Lung clearance index was more abnormal in PCD patients with microtubular defects (median 10.24) than those with dynein arm defects (median 8.3, p = 0.004) or normal ultrastructure (median 7.63, p = 0.0004). Age is correlated with LCI, with older patients having worse LCI values (p = 0.03, r = 0.3). CONCLUSION: This study shows that cilia microtubular defects are associated with worse LCI in PCD than dynein arm defects or normal ultrastructure. The patient's age at testing is also associated with a higher LCI. Patients at greater risk of obstructive lung disease should be considered for more aggressive management. Differences between patient groups may potentially open avenues for novel treatments.

Lung Clearance Index (LCI) is Stable in Most Primary Ciliary Dyskinesia (PCD) Patients Managed in a Specialist Centre: a Pilot Study.

Primary ciliary dyskinesia is a condition in which abnormal cilia structure or function leads to reduced mucociliary clearance and obstructive lung disease. Twenty-nine patients had lung clearance index (LCI) measured in 2009 and we attempted to perform a 5-year follow-up. Only 12 patients could be re-recruited, but in this small group LCI was stable over the 5 years, which confirms previous data showing that spirometry is also stable in these patients over the medium term. The two patients with the highest LCI in 2009 had since died, despite one having relatively preserved spirometry at the time. These data may be used to inform sample size calculations of future studies.

Investigating what works to support family carers of people with dementia: a rapid realist review.

Introduction: Advances in longevity and medicine mean that many more people in the UK survive life-threatening diseases but are instead susceptible to life-limiting diseases such as dementia. Within the next 10 years those affected by dementia in the UK is set to rise to over 1 million, making reliance on family care of people with dementia (PWD) essential. A central challenge is how to improve family carer support to offset the demands made by dementia care which can jeopardise carers' own health. This review investigates 'what works to support family carers of PWD'. Methods: Rapid realist review of a comprehensive range of databases. Results: Five key themes emerged: (1) extending social assets, (2) strengthening key psychological resources, (3) maintaining physical health status, (4) safeguarding quality of life and (5) ensuring timely availability of key external resources. It is hypothesized that these five factors combine and interact to provide critical biopsychosocial and service support that bolsters carer 'resilience' and supports the maintenance and sustenance of family care of PWD. Conclusions: 'Resilience-building' is central to 'what works to support family carers of PWD'. The resulting model and Programme Theories respond to the burgeoning need for a coherent approach to carer support.

Biomarkers of Tolerance in Kidney Transplantation: Are We Predicting Tolerance or Response to Immunosuppressive Treatment?

We and others have previously described signatures of tolerance in kidney transplantation showing the differential expression of B cell-related genes and the relative expansions of B cell subsets. However, in all of these studies, the index group-namely, the tolerant recipients-were not receiving immunosuppression (IS) treatment, unlike the rest of the comparator groups. We aimed to assess the confounding effect of these regimens and develop a novel IS-independent signature of tolerance. Analyzing gene expression in three independent kidney transplant patient cohorts (232 recipients and 14 tolerant patients), we have established that the expression of the previously reported signature was biased by IS regimens, which also influenced transitional B cells. We have defined and validated a new gene expression signature that is independent of drug effects and also differentiates tolerant patients from healthy controls (cross-validated area under the receiver operating characteristic curve [AUC] = 0.81). In a prospective cohort, we have demonstrated that the new signature remained stable before and after steroid withdrawal. In addition, we report on a validated and highly accurate gene expression signature that can be reliably used to identify patients suitable for IS reduction (approximately 12% of stable patients), irrespective of the IS drugs they are receiving. Only a similar approach will make the conduct of pilot clinical trials for IS minimization safe and hence allow critical improvements in kidney posttransplant management.

Accelerating the search for global minima on potential energy surfaces using machine learning.

Controlling molecule-surface interactions is key for chemical applications ranging from catalysis to gas sensing. We present a framework for accelerating the search for the global minimum on potential surfaces, corresponding to stable adsorbate-surface structures. We present a technique using Bayesian inference that enables us to predict converged density functional theory potential energies with fewer self-consistent field iterations. We then discuss how this technique fits in with the Bayesian Active Site Calculator, which applies Bayesian optimization to the problem. We demonstrate the performance of our framework using a hematite (Fe2O3) surface and present the adsorption sites found by our global optimization method for various simple hydrocarbons on the rutile TiO2 (110) surface.

A realist synthesis of the evidence on outreach programmes for health improvement of Traveller Communities.

BACKGROUND: Improving the health of Traveller Communities is an international public health concern but there is little evidence on effective interventions. This study aimed to explain how, for whom and in what circumstances outreach works in Traveller Communities. METHODS: A realist synthesis was undertaken. Systematic literature searches were conducted between August and November 2011. Grey literature was sought and key stakeholders were involved throughout the review process. Iterative steps of data extraction, analysis and synthesis, followed by additional searches were undertaken. RESULTS: An explanatory framework details how, why and in what circumstances participation, behaviour change or social capital development happened. The trust status of outreach workers is an important context of outreach interventions, in conjunction with their ability to negotiate the intervention focus. The higher the outreach worker's trust status, the lower the imperative that they negotiate the intervention focus. A 'menu' of reasoning mechanisms is presented, leading to key engagement outcomes. CONCLUSIONS: Adopting a realist analysis, this study offers a framework with explanatory purchase as to the potential of outreach to improve health in marginalized groups.

Radiological study of the anatomy of the keystone area of the nasal septum using computed tomography to aid septal surgery.

OBJECTIVES: An optimum septoplasty result may require complete detachment of the superior osseocartilaginous junction (OCJ), but this may lead to disruption of the keystone area with loss of nasal support and consequent supratip depression deformity. The aim of this study was to analyse normal keystone anatomy using CT scan images and to estimate the incidence of risk of supratip depression when completely detaching the OCJ. DESIGN: Retrospective study. SETTING: Tertiary referral centre. PARTICIPANTS: Adult patients who underwent CT paranasal sinuses prior to transsphenoidal hypophysectomy in a tertiary referral centre between 2009 and 2013. MAIN OUTCOME MEASURES: Length of the keystone area. A length of <5 mm and certain anatomical configurations were considered at risk of a supratip depression with complete detachment of the OCJ. RESULTS: CT scans of 91 patients were reviewed. The mean keystone length was 9.04 mm (range 0-23 mm). Twenty-nine (32%) cases were at risk of supratip depression. Relatively shorter nasal bones (nasal bone length: overall dorsal length <0.37) (n = 26) were associated with a shorter keystone area (P = 0.0051). CONCLUSIONS: Thirty-two per cent of patients have keystone anatomy on radiology predisposing them to supratip depression with complete detachment of the OCJ. Relatively shorter nasal bones were significantly associated with a shorter, higher risk keystone area. In cases with a high septal deviation undergoing a septoplasty, a preoperative CT enables the surgeon to assess the keystone area and determine whether it is safe to completely detach the OCJ.

An epidemiological study to investigate the relationship between Meniere's disease and migraine.

OBJECTIVES: A relationship between Meniere's disease and migraine has been postulated previously. This study investigates this relationship further and determines the most influential factors for developing Meniere's disease. DESIGN: Epidemiological study. SETTING: Two tertiary referral Neuro-Otological centres in Sheffield and Sydney. PARTICIPANTS: Adult patients referred to the Neuro-Otology clinic between 2003 and 2010. MAIN OUTCOME MEASURES: Past history and family history of Meniere's disease and migraine. Logistic regression analysis to determine the most influential factors for Meniere's disease. RESULTS: One hundred and eighty-one patients were included in the study, 102 with Meniere's disease and 79 with other balance disorders. Three significant findings were demonstrated. Firstly, a family history of Meniere's disease (33.3% versus 6.3%) or migraine (21.6% versus 9%) is more common in the Meniere's disease group than in the other balance disorders group. Secondly, a history of migrainous headaches is more common in the Meniere's disease group than in the other balance disorders group (45.1% versus 9%). Thirdly, patients with a past history or a family history of Meniere's disease or migraine have a higher likelihood of suffering from Meniere's disease. CONCLUSIONS: There is an overall relationship between Meniere's disease and migraine. A family history of Meniere's disease or migraine is more common in Meniere's disease. A history of migrainous headache is more common in Meniere's disease. Patients with a past history or family history of Meniere's disease or migraine have a higher likelihood of suffering from Meniere's disease.

Scanning capacitance microscopy registration of buried atomic-precision donor devices.

We show that a scanning capacitance microscope (SCM) can image buried delta-doped donor nanostructures fabricated in Si via a recently developed atomic-precision scanning tunneling microscopy (STM) lithography technique. A critical challenge in completing atomic-precision nanoelectronic devices is to accurately align mesoscopic metal contacts to the STM defined nanostructures. Utilizing the SCMs ability to image buried dopant nanostructures, we have developed a technique by which we are able to position metal electrodes on the surface to form contacts to underlying STM fabricated donor nanostructures with a measured accuracy of 300 nm. Low temperature (T = 4 K) transport measurements confirm successful placement of the contacts to the donor nanostructures.

Can lay health trainers increase uptake of NHS Health Checks in hard-to-reach populations? A mixed-method pilot evaluation.

BACKGROUND: The NHS Health Check Programme was launched in England in 2009, offering a vascular risk assessment to people aged 40-74 years without established disease. Socio-economic deprivation is associated with higher risk of cardiovascular disease and lower uptake of screening. We evaluated the potential impact of a community-based health check service that sought to address health inequalities through the involvement of lay health trainers. METHODS: Key stakeholder discussions (n = 20), secondary analysis of client monitoring data (n = 774) and patient experience questionnaires (n = 181). RESULTS: The health check programme was perceived as an effective way of engaging people in conversations about their health. More than half (57.6%) of clients were aged under 50 years and a similar proportion (60.5%) were from socio-economically deprived areas. Only 32.7% from the least affluent areas completed a full health check in comparison with 44.4% from more affluent areas. Eligible men were more likely than eligible women to complete a health check (59.4 versus 33.8%). CONCLUSIONS: A community-based, health trainer-led approach may add value by offering an acceptable alternative to health checks delivered in primary care settings. The service appeared to be particularly successful in engaging men and younger age groups. However, there exists the potential for intervention-generated inequalities.

Investigating the use of the neutropenic diet: a survey of U.K. dietitians.

BACKGROUND: Patients with chemotherapy-induced neutropenia are at increased risk of infection. Historically, dietary restrictions commonly referred to as 'clean', 'low bacteria', 'low-microbial' or 'neutropenic' diets have been prescribed to reduce the risk of foodborne infection. Although research does not support their effectiveness, they continue to be used in clinical practice. The present study aimed to investigate the use of dietary restrictions in patients with cancer in the UK by surveying registered dietitians (RDs). METHODS: An online questionnaire was distributed to 573 RDs via local and specialist interest groups of the British Dietetic Association. RESULTS: One hundred and ten questionnaires were returned. Of these, 67.8% of RDs prescribed dietary restrictions to patients, with 'neutropenic diet' being the most commonly used term. Specialist oncology or haematology RDs were more likely to use the diet than nonspecialist RDs (P < 0.005). The variety of foods restricted varied greatly and was often contradicting. Unpasteurised dairy products and raw or lightly cooked meat or fish were most commonly restricted. Less than half (43.6%) of RDs had a policy in place for the use of neutropenic diets, with specialist oncology and haematology RDs more likely to report this (P < 0.005). CONCLUSIONS: Neutropenic dietary advice provided by dietitians in the UK varies greatly. Further high-quality research is required to create an evidence base from which national clinical guidelines can be formed.

The association between postprandial urinary C-peptide creatinine ratio and the treatment response to liraglutide: a multi-centre observational study.

AIMS: The response to glucagon-like peptide 1 receptor agonist treatment may be influenced by endogenous ß-cell function. We investigated whether urinary C-peptide creatinine ratio assessed before or during liraglutide treatment was associated with treatment response. METHODS: A single, outpatient urine sample for urinary C-peptide creatinine ratio was collected 2 h after the largest meal of the day among two separate groups: (1) subjects initiating liraglutide (0.6 â†’ 1.2 mg daily) or (2) subjects already treated with liraglutide for 20-32 weeks. The associations between pretreatment and on-treatment urinary C-peptide creatinine ratio and HbA1c change at 32 weeks were assessed using univariate and multivariate analyses (the ratio was logarithm transformed for multivariate analyses). Changes in HbA1c according to pretreatment urinary C-peptide creatinine ratio quartiles are shown. RESULTS: One hundred and sixteen subjects (70 pretreatment, 46 on treatment) with Type 2 diabetes from 10 diabetes centres were studied. In univariate analyses, neither pretreatment nor on-treatment urinary C-peptide creatinine ratio correlated with HbA1c change (Spearman rank correlation coefficient, r = -0.17, P = 0.17 and r = -0.20, P = 0.19, respectively). In multi-linear regression analyses, entering baseline HbA1c and log urinary C-peptide creatinine ratio, pretreatment and on-treatment log urinary C-peptide creatinine ratio became significantly associated with HbA1c change (P = 0.048 and P = 0.040, respectively). Mean (sd) HbA1c changes from baseline in quartiles 1 to 4 of pretreatment urinary C-peptide creatinine ratio were -3 ± 17 mmol/mol (-0.3 ± 1.6%) (P = 0.52), -12 ± 15 mmol/mol (-1.1 ± 1.4%) (P = 0.003), -11 ± 13 mmol/mol (-1.0 ± 1.2%) (P = 0.002) and -12±17 mmol/mol (-1.1±1.6%) (P=0.016), respectively. CONCLUSIONS: Postprandial urinary C-peptide creatinine ratios before and during liraglutide treatment were weakly associated with the glycaemic response to treatment. Low pretreatment urinary C-peptide creatinine ratio may be more useful than higher values by predicting poorer glycaemic response.

Analysis of the kinetics and yields of OH radical production from the CH3OCH2 + O2 reaction in the temperature range 195-650 K: an experimental and computational study.

The methoxymethyl radical, CH3OCH2, is an important intermediate in the low temperature combustion of dimethyl ether. The kinetics and yields of OH from the reaction of the methoxymethyl radical with O2 have been measured over the temperature and pressure ranges of 195-650 K and 5-500 Torr by detecting the hydroxyl radical using laser-induced fluorescence following the excimer laser photolysis (248 nm) of CH3OCH2Br. The reaction proceeds via the formation of an energized CH3OCH2O2 adduct, which either dissociates to OH + 2 H2CO or is collisionally stabilized by the buffer gas. At temperatures above 550 K, a secondary source of OH was observed consistent with thermal decomposition of stabilized CH3OCH2O2 radicals. In order to quantify OH production from the CH3OCH2 + O2 reaction, extensive relative and absolute OH yield measurements were performed over the same (T, P) conditions as the kinetic experiments. The reaction was studied at sufficiently low radical concentrations (∼10(11) cm(-3)) that secondary (radical + radical) reactions were unimportant and the rate coefficients could be extracted from simple bi- or triexponential analysis. Ab initio (CBS-GB3)/master equation calculations (using the program MESMER) of the CH3OCH2 + O2 system were also performed to better understand this combustion-related reaction as well as be able to extrapolate experimental results to higher temperatures and pressures. To obtain agreement with experimental results (both kinetics and yield data), energies of the key transition states were substantially reduced (by 20-40 kJ mol(-1)) from their ab initio values and the effect of hindered rotations in the CH3OCH2 and CH3OCH2OO intermediates were taken into account. The optimized master equation model was used to generate a set of pressure and temperature dependent rate coefficients for the component nine phenomenological reactions that describe the CH3OCH2 + O2 system, including four well-skipping reactions. The rate coefficients were fitted to Chebyshev polynomials over the temperature and density ranges 200 to 1000 K and 1 × 10(17) to 1 × 10(23) molecules cm(-3) respectively for both N2 and He bath gases. Comparisons with an existing autoignition mechanism show that the well-skipping reactions are important at a pressure of 1 bar but are not significant at 10 bar. The main differences derive from the calculated rate coefficient for the CH3OCH2OO → CH2OCH2OOH reaction, which leads to a faster rate of formation of O2CH2OCH2OOH.

ECFS standards of care on CFTR-related disorders: Towards a comprehensive program for affected individuals.

After three publications defining an updated guidance on the diagnostic criteria for people with cystic fibrosis transmembrane conductance regulator (CFTR)-related disorders (pwCFTR-RDs), establishing its relationship to CFTR-dysfunction and describing the individual disorders, this fourth and last paper in the series addresses some critical challenges facing health care providers and pwCFTR-RD. Topics included are: 1) benefits and obstacles to collect data from pwCFTR-RD are discussed, together with the opportunity to integrate them into established CF-registries; 2) the potential of infants designated CRMS/CFSPID to develop a CFTR-RD and how to communicate this information; 3) a description of the challenges in genetic counseling, with particular regard to phenotypic variability, unknown long-term evolution, CFTR testing and pregnancy termination 4) a proposal for the assessment of potential barriers to the implementation and dissemination of the produced documents to health care professionals involved in the care of pwCFTR-RD and a process to monitor the implementation of the CFTR-RD recommendations; 5) clinical trials investigating the efficacy of CFTR modulators in CFTR-RD and how endpoints and outcomes might be adapted to the heterogeneity of these disorders.