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.

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.

Central Slip Repair using Trans-articular K-wires: A Comparative Study.

Central slip disruption may lead to PIP joint dysfunction causing significant morbidity. Existing evidence for any specific surgical management of these injuries is limited but does favor early mobilization of the PIP joint. Aim: To assess the functional outcome in a cohort of patients undergoing central slip repair with internal K-wire proximal interphalangeal joint splinting and complete immobilization against those with external splinting only. Methods: A single center retrospective analysis of all patients that underwent operative central slip repair in our institution over a 5-year period. Data were collected via the HIPE database and clinical notes. Data relating to demographics as well as range of motion, total active motion {(TAM) (TAM%)} score, and hand therapy rehabilitation type were analyzed. Results: The study population was n = 44 patients. N = 33 patients were treated without a K-wire and n = 11 treated with a K-wire. There was a male predominance, 81.8% (n = 36). Mean age was 40.4 years. There was no significant difference in the mean TAM achieved at final measurement between the "no K-wire" and the "K-wire" treatment groups [no K-wire 202.1° (standard deviations (SD) 40.0) vs. K-wire 187.4° (SD 28.2), p = 0.208]. The "no K-wire group" achieved a mean TAM % of 78.0 (SD 11.4) and the "K-wire group" achieved a mean TAM % of 72.1 (SD 10.8); no statistically significant difference in mean scores was observed between groups. Conclusion: Our study has shown comparable functional outcomes between those having complete joint immobilization with internal K-wire splinting and those that are externally splinted only following central slip repair.

Impact of elexacaftor/tezacaftor/ivacaftor on fat-soluble vitamin levels in children with cystic fibrosis.

BACKGROUND: Children with cystic fibrosis are at risk of fat-soluble vitamin deficiency. CFTR modulators positively effect nutritional status. This study aimed to assess changes in serum vitamins A, D & E after starting ETI therapy to ensure levels were not abnormally high. METHODS: Retrospective review of annual assessment data over 3½ years, before and after starting ETI in a specialist paediatric CF centre, including vitamin levels. RESULTS: 54 eligible patients were included, aged 5-15 yrs (median age 11.5). Median time to post measurements was 171 days. Median vitamin A was increased (1.38 to 1.63 µmol/L, p<0.001). Three patients (6%) had high vitamin A post-ETI, compared with none at baseline; and 2 (4%) had low levels compared to 4 (8%) at baseline. No changes in vitamins D&E. CONCLUSIONS: This study found increased vitamin A, sometimes to high levels. We recommend testing levels within 3 months of starting ETI.

A novel 3D volumetric method for directly quantifying porosity and pore space morphology in flocculated suspended sediments.

Flocculated suspended sediments (flocs) are found in a variety of environments globally, and their transport and behavior bear substantial importance to several industries including fisheries, aquaculture, and shipping. Additionally, the modelling of their behavior is important for estuarine and coastal flood prediction and defence, and the process of flocculation occurs in other unrelated industries such as paper and chemical production. Floc porosity is conventionally assessed using inferential indirect or proxy data approaches. These methods underestimate floc porosity % by c. 30% and cannot measure the micro-scale complexity of these pore spaces and networks, rendering inputs to models sub-optimal. This study introduces a novel 3D porosity and pore space quantification protocol, that produces directly quantified porosity % and pore space data.•3D floc data from micro-CT scanning is segmented volumetrically•This segmented volume is quantified to extract porosity and several pore space parameters from the floc structure.

Quantification of 3-dimensional structure and properties of flocculated natural suspended sediment.

Natural sediment flocs are fragile and highly heterogeneous aggregates of biogenic and minerogenic material typically with high porosity and low density. In aquatic environments dominated by fine, cohesive or mixed sediments they can dominate suspended sediment flux. Consequently, monitoring and modelling the behaviour, transport and distribution of flocs is very important for many aquatic industries, maintenance of waterways and conservation and management of aquatic waterbodies. Mathematical models that predict the behaviour of flocs rely on the accurate assessments of the size, shape, density, porosity and fractal dimension of flocs. These inherently 3-dimensional (3D) characteristics are typically derived from 2-dimensional (2D) data, largely due to the challenges associated with sampling, capturing, imaging and quantifying these fragile aggregates. We have developed new volumetric microscopy techniques which can quantify 3D internal and external structures and characteristics of sediment flocs. Here, these techniques were applied to quantify the 3D size (volume), shape and fractal dimension of natural and artificial sediment flocs and compare them to standard 2D approaches. Our study demonstrates that 2D approaches are under-estimating shape complexity and over-estimating the size and mass settling flux of flocs by up to two orders of magnitude, and the discrepancy between 2D and 3D is most marked for natural, organic rich macroflocs. Our study has significant implications for estimations of sediment flux at local to global scales within in aquatic environments. These new data and approaches offer the potential to improve the current parameterisation of sediment transport models and to improve the accuracy of current field-monitoring techniques.

Acellular dermal substitute use in the reconstruction of axillary hidradenitis suppurativa.

Hidradenitis suppurativa (HS) is a chronic recurrent debilitating condition that affects the skin near to the follicular glands. The disease manifests with the formation of abscesses that can be complicated by rupture, sinus tracts, and scarring leading to pain, chronic discharge, malodor, and scar contractures. The management of HS is multidisciplinary, involving general lifestyle modification, medical treatment, and surgery. A wide range of surgical interventions has been described for HS disease control and management. However, surgical management strategies are highly variable. We describe the case of a 33-year-old female with refractory HS which was reconstructed with Matriderm® and an immediate split-thickness skin graft. Acellular dermal skin substitutes may be an alternative to conventional means of HS reconstruction, producing subtle, pliable, and durable skin.

Facilitating social coping-'seeking emotional and practical support from others'-as a critical strategy in maintaining the family care of people with dementia.

The aim of this study was to identify how the family care of people living with dementia could be supported to make reliance on family care sustainable in the long term despite the impact of stress. A Realist Evaluation (Pawson & Tilley, 1997) was conducted to investigate this aim. An initial review established 'coping' as a primary means of mediating stressors associated with caregiving. However, there was a need to specify which coping approaches/strategies are most effective. In-depth interviews were conducted with a purposive sample of family carers (n = 18) in a suburb in North East England from 2016 to 2017. Analysis of the data revealed 'social coping' (SC) that included an emotional support component as a critical mediator of family carer stress. Several key hindrances to the utilisation of SC, including underpinning causal factors, are explicated. Ways in which these hindrances might be overcome are discussed and guidelines introduced for how family carers, formal providers and practitioners can facilitate SC as a critical coping strategy in sustaining the family care of people with dementia over the long term.

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.

Atypical facial presentation of subcutaneous fat necrosis of the newborn.

Subcutaneous fat necrosis of the newborn (SCFN) is a rare self-limiting panniculitis. It is thought to be associated with perinatal hypoxia and therapeutic hypothermia. It is characterised by firm subcutaneous nodules on the back, shoulder and arms. We present a rare facial presentation of SCFN in a 4-week-old infant with no history of therapeutic cooling. She presented with a discrete right cheek mass with no overlying skin changes. We present the diagnostic challenge and undertake a review of the literature. SCFN is an important differential diagnosis in a neonate with subcutaneous facial lesions. SCFN can be complicated by metabolic derangements including hypercalcaemia.

Camptodactyly and DiGeorge syndrome: A rare hand anomaly.

The most common deletion syndrome is 22q11.2 and it effects an estimated 1 in 3000 live births. Major features of this multisystem condition include congenital abnormalities, developmental delay, learning difficulties, immunodeficiency, endocrine anomalies and an array of psychiatric disorders. However, variability in phenotype and severity may cause the diagnosis to be overlooked. Early clinical recognition and treatment of DiGeorge syndrome has been shown to increase early life survival, decrease complications and enhance overall quality of life. Skeletal anomalies are infrequently described in 22q11.2 but a subset of patients exhibit upper and lower limb deformities. We present the case of a 5 year-old girl with bilateral fifth digit camptodactyly caused by a fibrous band, and the surgical management of this condition. The current report adds to the body of evidence that camptodactyly is a rare clinical feature of 22q11.2 deletion syndrome, and may serve as a diagnostic aid in these patients.

Optimising equity of access: how should we allocate slots to the most competitive trials in Cystic Fibrosis (CF)?

BACKGROUND: Trial participation can allow people with CF early access to CFTR modulator therapies, with high potential for clinical benefit. Therefore, the number of people wishing to participate can substantially exceed the number of slots available. We aimed to understand how the CF community thinks slots to competitive trials should be allocated across the UK and whether this should be driven by clinical need, patients' engagement/adherence or be random. For the latter, we explored site-level versus registry-based, national randomisation processes. METHODS: We developed an online survey, recruiting UK-based stakeholders through social media, newsletters and personal contacts. Closed questions were analysed for frequencies and percentages of responses. Free-text questions were analysed using thematic analysis. RESULTS: We received 203 eligible responses. Overall, 75% of stakeholders favoured allocation of slots to individual sites based on patient population size, although pharma favoured allocation based on previous metrics. Currently, few centres have defined strategies for allocating slots locally. At face-value, stakeholders believe all eligible participants should have an equal chance of getting a slot. However, further questioning reveals preference for prioritisation strategies, primarily perceived treatment adherence, although healthcare professionals were less likely to favour this strategy than other stakeholder groups. The majority of stakeholders would prefer to allocate slots and participate in trials locally but 80% said if necessary, they would engage in a system of national allocation. CONCLUSIONS: Fair allocation to highly competitive trials does not appear to have a universally acceptable solution. Therefore, transparency and empathy remain critical to negotiate this uncertain territory.

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.

CSACI guidelines for the ethical, evidence-based and patient-oriented clinical practice of oral immunotherapy in IgE-mediated food allergy.

BACKGROUND: Oral immunotherapy (OIT) is an emerging approach to the treatment of patients with IgE-mediated food allergy and is in the process of transitioning to clinical practice. OBJECTIVE: To develop patient-oriented clinical practice guidelines on oral immunotherapy based on evidence and ethical imperatives for the provision of safe and efficient food allergy management. MATERIALS AND METHODS: Recommendations were developed using a reflective patient-centered multicriteria approach including 22 criteria organized in five dimensions (clinical, populational, economic, organizational and sociopolitical). Data was obtained from: (1) a review of scientific and ethic literature; (2) consultations of allergists, other healthcare professionals (pediatricians, family physicians, nurses, registered dieticians, psychologists, peer supporters), patients and caregivers; and patient associations through structured consultative panels, interviews and on-line questionnaire; and (3) organizational and economic data from the milieu of care. All data was synthesized by criteria in a multicriteria deliberative guide that served as a platform for structured discussion and development of recommendations for each dimension, based on evidence, ethical imperatives and other considerations. RESULTS: The deliberative grid included 162 articles from the literature and media reviews and data from consultations involving 85 individuals. Thirty-eight (38) recommendations were made for the practice of oral immunotherapy for the treatment of IgE mediated food allergy, based on evidence and a diversity of ethical imperatives. All recommendations were aimed at fostering a context conducive to achieving objectives identified by patients and caregivers with food allergy. Notably, specific recommendations were developed to promote a culture of shared responsibility between patients and healthcare system, equity in access, patient empowerment, shared decision making and personalization of OIT protocols to reflect patients' needs. It also provides recommendations to optimize organization of care to generate capacity to meet demand according to patient choice, e.g. OIT or avoidance. These recommendations were made acknowledging the necessity of ensuring sustainability of the clinical offer in light of various economic considerations. CONCLUSIONS: This innovative CPG methodology was guided by patients' perspectives, clinical evidence as well as ethical and other rationales. This allowed for the creation of a broad set of recommendations that chart optimal clinical practice and define the conditions required to bring about changes to food allergy care that will be sustainable, equitable and conducive to the well-being of all patients in need.

Demonstrating reliability through transparency: A scientific validity framework to assist scientists and lawyers in criminal proceedings.

In recent decades, forensic science evidence has come to play an increasingly significant role in criminal proceedings. However, the ability of non-scientists (lay-persons, including lawyers and judges) within criminal justice systems to recognise and resolve issues of validity and reliability relating to expert opinion evidence has not maintained pace with the need to do so. Despite international scrutiny from scientists, statisticians, governments and those involved in law reform, the parameters of a) different forensic disciplines and b) some case specific interpretations, remain elusive to some legal practitioners and judges. It is therefore essential that within the context of national, and increasingly international and transnational criminal investigations, forensic science experts convey the evidential value of the scientific findings in a manner that is understandable to, and useable by all. To assist, this paper first identifies the organisational structures necessary to scaffold and support the delivery of reliable expert opinion evidence. This is followed by a format for transparently reporting the reasoning and the scientific validity underpinning the expert's evidence within their report: a tripartite Scientific Validity Framework. This framework is comprised of (i) foundational validity, (ii) applied validity and (iii) the new concept of evaluative validity. Such a framework, because of its underlying scientific principles, is applicable to expert reports in any jurisdiction and is complementary to different national approaches. That is because utilising this framework could ensure that experts can, and do, demonstrate that their case-specific opinion is reliable and alert the legal profession to the expert's reasoning process and any limitations in the scientific validity underpinning the opinion.

Single-Shot Readout Performance of Two Heterojunction-Bipolar-Transistor Amplification Circuits at Millikelvin Temperatures.

High-fidelity single-shot readout of spin qubits requires distinguishing states much faster than the T1 time of the spin state. One approach to improving readout fidelity and bandwidth (BW) is cryogenic amplification, where the signal from the qubit is amplified before noise sources are introduced and room-temperature amplifiers can operate at lower gain and higher BW. We compare the performance of two cryogenic amplification circuits: a current-biased heterojunction bipolar transistor circuit (CB-HBT), and an AC-coupled HBT circuit (AC-HBT). Both circuits are mounted on the mixing-chamber stage of a dilution refrigerator and are connected to silicon metal oxide semiconductor (Si-MOS) quantum dot devices on a printed circuit board (PCB). The power dissipated by the CB-HBT ranges from 0.1 to 1 µW whereas the power of the AC-HBT ranges from 1 to 20 µW. Referred to the input, the noise spectral density is low for both circuits, in the 15 to 30 fA/[Formula: see text] range. The charge sensitivity for the CB-HBT and AC-HBT is 330 µe/[Formula: see text] and 400 µe/[Formula: see text], respectively. For the single-shot readout performed, less than 10 µs is required for both circuits to achieve bit error rates below 10-3, which is a putative threshold for quantum error correction.