Subglottic cysts: The Great Ormond Street experience in 105 patients.

PURPOSE: The aim of the study was to assess the contemporary presentation and management of subglottic cysts and make recommendations on the treatment of these patients. METHODS: Retrospective case series of 105 patients between October 1999 and November 2017 from a paediatric teaching hospital. RESULTS: Ninety-one percentage (n = 96) had a history of prematurity, with a mean gestation of 27.2 weeks (SD ± 4.1). A history of intubation was found in 99% (n = 104) of cases [median 18 days (range = 1-176)]. Presenting symptoms were: Stridor 57.1%, (n = 60), difficult intubation 14% (n = 15), recurrent croup 11.4% (n = 12), failed extubation 7.6%, (n = 8), hoarseness/weak cry 10.5% (n = 10). Ninety percentage (n = 94) underwent intervention for management of SGCs with 86% (n = 81) treated with cold steel marsupialisation and 14% (n = 13) with CO 2 laser. Recurrent cysts occurred in 56% (n = 53) of cases. Treatment modality did not affect recurrence (p = 0.594 Δ). Sixty-six percentage (n = 69/105) of patients had one or more concurrent airway pathology at MLB. Most frequent was subglottic stenosis 47% (n = 49), with 16% (n = 8) subsequently requiring open reconstructive airway surgery. Mean duration of follow-up was 47.6 months (SD ± 38.3). CONCLUSION: SGC are an uncommon, reversible cause of upper airway obstruction and should be considered in the list of differential diagnoses in patients with a history of prematurity and perinatal intubation, presenting with stridor. While concurrent SGS is common, adequate symptom improvement in such cases may be achieved with SGC removal alone. Management is by surgical marsupialisation. Recurrence and additional airway pathologies are common and may necessitate longer-term treatment in centres with paediatric airway expertise.

Interprofessional education clinical placement program: a qualitative case study approach.

The goal of health professional education programs is to produce competent graduates, with an ability to work collaboratively as effective healthcare team members. We explored the reflections of students and clinical facilitators, in response to participation in a structured interprofessional education (IPE) clinical placement program. In our qualitative study we used an exploratory case study design. In our analysis, we highlight the benefits of interprofessional practice. Key themes identified by students included: limited opportunities to engage in IPE across their course; lack of clarity around IPE; value of IPE for students, practitioners, and patient outcomes; and need for IPE opportunities to be integrated into placements. Key themes identified by the clinical facilitators included: being reminded of the value of IPE for students and patients; preparation for IPE placements need to be embedded in curricula; coordination and communication of IPE learning activities need to be clear for staff and students; and IPE should continue as part of the broader clinical education agenda. Our findings reinforce the notion that students and clinical facilitators value the importance of IPE for student learning within the clinical placement setting. The outcomes offer valuable insights for universities and hospital and health care contexts for setting up and implementing IPE activities, and we provide recommendations for improving ongoing IPE efforts within clinical placement setting.

A review of the safety of MRI in cochlear implant patients with retained magnets.

The number of patients with cochlear implants (CIs) is increasing due to expanding indications, and improving CI services. Furthermore, as the use of imaging increases in clinical medicine, it is increasingly likely that patients with CIs will require a magnetic resonance imaging (MRI) examination during their lifetime. Therefore it is important that clinicians are aware of the safety aspects and manufacturer recommendations for CI patients with retained magnets. This article summarises guidelines from all major CI manufacturers and reviews the published literature on the safety of MRI in CI patients with magnets in situ. The most commonly reported complication of MRI in CI patients was pain. Other significant complications included magnet displacement, depolarisation, and polarity reversal. Artefacts caused by the CI remain an issue, but may be reduced by the use of specific sequences. Manufacturer recommendations should be followed to reduce the risk of complications, although complications may occur even when guidelines are followed. For this reason, the indication for imaging these patients should be reviewed, and patients should be appropriately counselled and consented.

Microplastics in Sewage Sludge: Effects of Treatment.

Waste water treatment plants (WWTPs) are receptors for the cumulative loading of microplastics (MPs) derived from industry, landfill, domestic wastewater and stormwater. The partitioning of MPs through the settlement processes of wastewater treatment results in the majority becoming entrained in the sewage sludge. This study characterized MPs in sludge samples from seven WWTPs in Ireland which use anaerobic digestion (AD), thermal drying (TD), or lime stabilization (LS) treatment processes. Abundances ranged from 4196 to 15 385 particles kg-1 (dry weight). Results of a general linear mixed model (GLMM) showed significantly higher abundances of MPs in smaller size classes in the LS samples, suggesting that the treatment process of LS shears MP particles. In contrast, lower abundances of MPs found in the AD samples suggests that this process may reduce MP abundances. Surface morphologies examined using scanning electron microscopy (SEM) showed characteristics of melting and blistering of TD MPs and shredding and flaking of LS MPs. This study highlights the potential for sewage sludge treatment processes to affect the risk of MP pollution prior to land spreading and may have implications for legislation governing the application of biosolids to agricultural land.

A simulation-based approach for estimating the time-dependent reproduction number from temporally aggregated disease incidence time series data.

Tracking pathogen transmissibility during infectious disease outbreaks is essential for assessing the effectiveness of public health measures and planning future control strategies. A key measure of transmissibility is the time-dependent reproduction number, which has been estimated in real-time during outbreaks of a range of pathogens from disease incidence time series data. While commonly used approaches for estimating the time-dependent reproduction number can be reliable when disease incidence is recorded frequently, such incidence data are often aggregated temporally (for example, numbers of cases may be reported weekly rather than daily). As we show, commonly used methods for estimating transmissibility can be unreliable when the timescale of transmission is shorter than the timescale of data recording. To address this, here we develop a simulation-based approach involving Approximate Bayesian Computation for estimating the time-dependent reproduction number from temporally aggregated disease incidence time series data. We first use a simulated dataset representative of a situation in which daily disease incidence data are unavailable and only weekly summary values are reported, demonstrating that our method provides accurate estimates of the time-dependent reproduction number under such circumstances. We then apply our method to two outbreak datasets consisting of weekly influenza case numbers in 2019-20 and 2022-23 in Wales (in the United Kingdom). Our simple-to-use approach will allow accurate estimates of time-dependent reproduction numbers to be obtained from temporally aggregated data during future infectious disease outbreaks.

Pitfalls of operative management of secondary post-tonsillectomy haemorrhage--a case report.

INTRODUCTION: The authors present a potential complication associated with the surgical management of post-tonsillectomy haemorrhage using absorbable cellulose haemostatic dressings. The article discusses the deficiencies of our current understanding of how best to manage this common and potentially life-threatening ENT emergency. CASE REPORT: A 40-year-old man presented to Accident-and-Emergency with a post-tonsillectomy haemorrhage on the 7th postoperative day. The bleeding was managed surgically, with suturing of the faucial pillars incorporating a piece of Surgicel into the closure. Two days later the patient experienced an episode of partial airway obstruction, due to a piece of dislodged haemostatic material, owing to failure of the closure. The techniques used in the operative management of post-tonsillectomy bleeding are not formally evaluated or discussed in the current literature, and in some cases are unreliable or even potentially hazardous. Further discussion, research, and formulation of a more stepwise approach would be of considerable benefit.

A prospective, randomized, controlled trial of autologous haematopoietic stem cell transplantation for aggressive multiple sclerosis: a position paper.

BACKGROUND: Haematopoietic stem cell transplantation (HSCT) has been tried in the last 15 years as a therapeutic option in patients with poor-prognosis autoimmune disease who do not respond to conventional treatments. Worldwide, more than 600 patients with multiple sclerosis (MS) have been treated with HSCT, most of them having been recruited in small, single-centre, phase 1-2 uncontrolled trials. Clinical and magnetic resonance imaging outcomes from case series reports or Registry-based analyses suggest that a major response is achieved in most patients; quality and duration of response are better in patients transplanted during the relapsing-remitting phase than in those in the secondary progressive stage. OBJECTIVES: An interdisciplinary group of neurologists and haematologists has been formed, following two international meetings supported by the European and American Blood and Marrow Transplantation Societies, for the purpose of discussing a controlled clinical trial, to be designed within the new scenarios of evolving MS treatments. CONCLUSIONS: Objectives of the trial, patient selection, transplant technology and outcome assessment were extensively discussed. The outcome of this process is summarized in the present paper, with the goal of establishing the background and advancing the development of a prospective, randomized, controlled multicentre trial to assess the clinical efficacy of HSCT for the treatment of highly active MS.

Run-and-tumble particles with hydrodynamics: sedimentation, trapping, and upstream swimming.

We simulate by lattice Boltzmann the nonequilibrium steady states of run-and-tumble particles (inspired by a minimal model of bacteria), interacting by far-field hydrodynamics, subject to confinement. Under gravity, hydrodynamic interactions barely perturb the steady state found without them, but for particles in a harmonic trap such a state is quite changed if the run length is larger than the confinement length: a self-assembled pump is formed. Particles likewise confined in a narrow channel show a generic upstream flux in Poiseuille flow: chiral swimming is not required.

High resolution array analysis: diagnosing pregnancies with abnormal ultrasound findings.

BACKGROUND: Genome-wide high resolution array analysis is becoming established as a diagnostic test in the investigation of individuals with learning disability and congenital anomalies; many novel microdeletion and microduplication syndromes have already been identified. The diagnostic use of high resolution array genomic hybridisation analysis for prenatal testing remains to be systematically assessed. METHODS: We studied 106 prenatal samples with abnormal ultrasound and a normal karyotype using the Affymetrix GeneChip 6.0 array. "Rare" DNA copy number variations (CNVs) were classified into three groups depending on their size, genomic location and the presence or absence of matched copy number changes in a large cohort of 3000 control samples analysed for copy number changes using genotyping arrays. RESULTS: A total of 35 rare CNVs were identified. 10 (9%) of these are considered likely to represent pathogenic CNVs; 5 were syndromic and 5 were novel. 12 CNVs were detected in at least one control hybridisation and likely to be benign, and 13 CNVs were of unknown clinical significance. In addition, we identified one case of cryptic mosaicism for trisomy 10, one case of loss of heterozygosity (LOH), and showed that the Affymetrix GeneChip 6.0 array platform can detect triploidy. CONCLUSIONS: We conclude that careful implementation of high resolution array testing would benefit at least 10% of obstetric patients with abnormal ultrasound findings and a normal karyotype result.

Breast cancer invasion is mediated by beta-N-acetylglucosaminidase (beta-NAG) and associated with a dysregulation in the secretory pathway of cancer cells.

The extracellular matrix is enriched with carbohydrate polymers that mask the protein backbone. This study aims to test the hypothesis that for successful cancer cell invasion the cells must secrete glycosidases to reveal the protein backbone, and then the action of proteases provides the physical space needed for cancer cell movement. Thus, the activity of intracellular and secreted beta-N-acetylglucosaminidase (beta-NAG) was assayed in luminal breast epithelial cells (HB4a) and breast cancer cells (BT474, ZR75-1, MDA-MB-435, MCF7). An increase in the V(max) of beta-NAG was observed in MDA-MB-435 and MCF7 cells. Exoglycosidases are normally located in the lysosomes and function at an acidic pH, but in the cancer cells there was significant enzyme activity at neutral pH. A change in lysosome location and number was observed in the cancer cells, consistent with alterations in the secretory pathway. Finally, applying a cocktail of protease inhibitors resulted in a 20% reduction in invasion of MDA-MB-435 cells through Matrigel after 24 h, and when the cells were treated with protease and beta-NAG inhibitors then cellular invasion was reduced by > 60%. The results suggest combination therapies that inhibit proteases and glycosidases might be a rational way forward for the design of drugs aimed at arresting cellular invasion.

Development, validation and field application of an RNA-based growth index in juvenile plaice Pleuronectes platessa.

A general mechanism relating RNA concentration and growth rate is derived from four physiological assumptions and developed into a growth index for juvenile plaice Pleuronectes platessa. The index describing instantaneous growth rates (G, day⁻¹) in the laboratory with the lowest Akaike information criterion with small-sample bias adjustment was a function of RNA concentration (R, g(RNA)g⁻¹(wet mass)), temperature (T, ° K), body mass (M, g) and DNA concentration (D, g(DNA)g⁻¹(wet mass)): G = ß0 + ß(R) R + ß(T)T + ß(T2)T² + ß(M)M + ß(D)D + ß(RT)RT. RNA concentration began to respond to changes in feeding conditions within 8 days, suggesting that the index reflects growth rate in the short-term. Furthermore, the index distinguished between rapid growth and negative growth of juvenile P. platessa measured directly in laboratory and field enclosures, respectively. An application of the RNA-based growth index at two beaches on the west coast of Scotland suggested that the growth of juvenile P. platessa varies considerably in space and time and is submaximum in late summer.

Immunomodulatory effects of mixed hematopoietic chimerism: immune tolerance in canine model of lung transplantation.

Long-term survival after lung transplantation is limited by acute and chronic graft rejection. Induction of immune tolerance by first establishing mixed hematopoietic chimerism (MC) is a promising strategy to improve outcomes. In a preclinical canine model, stable MC was established in recipients after reduced-intensity conditioning and hematopoietic cell transplantation from a DLA-identical donor. Delayed lung transplantation was performed from the stem cell donor without pharmacological immunosuppression. Lung graft survival without loss of function was prolonged in chimeric (n = 5) vs. nonchimeric (n = 7) recipients (p < or = 0.05, Fisher's test). There were histological changes consistent with low-grade rejection in 3/5 of the lung grafts in chimeric recipients at > or =1 year. Chimeric recipients after lung transplantation had a normal immune response to a T-dependent antigen. Compared to normal dogs, there were significant increases of CD4+INFgamma+, CD4+IL-4+ and CD8+ INFgamma+ T-cell subsets in the blood (p < 0.0001 for each of the three T-cell subsets). Markers for regulatory T-cell subsets including foxP3, IL10 and TGFbeta were also increased in CD3+ T cells from the blood and peripheral tissues of chimeric recipients after lung transplantation. Establishing MC is immunomodulatory and observed changes were consistent with activation of both the effector and regulatory immune response.

Persistence of chlorinated hydrocarbon insecticides in soils.

The percentages of technical aldrin, chlordane, endrin, heptachlor, Dilan, isodrin, BHC, and toxaphene remaining in Congaree sandy loam soil after 14, years were 40, 40, 41, 16, 23, 15, 10, and 45, respectively; those of purified aldrin and technical dieldrin after 15 years were 28 and 31, respectively; and the percentage of technical DDT in three soils after 17 years was 39. Treatments and maintenance of the soils were such that leaching, volatilization, photodecomposition, mechanical removal, and probably biological decomposition were at a minimum. These values may approach an upper limit of persistence of insecticides in soil.

Chlorinated hydrocarbon insecticides: root uptake versus vapor contamination of soybean foliage.

The major environmental source of DDT (dichlorodiphenyltrichlo-roethane) residues in soybean plants arises from vapor movement from contaminated soil surfaces. In contrast, the presence of dieldrin, endrin, and heptachlor results primarily from root uptake and translocation through stems to leaves and seeds.

Ten years on from an appraisal of litigation against English Health Trusts in otolaryngology: What have we learnt?

NHS Resolution provides indemnity cover for legal claims against the NHS, assists the NHS with risk management and aims to share lessons from claims in order to improve safety. The study aimed to investigate the financial costs of litigation against English Health Trusts in otolaryngology over a 10-year period, to see if any lessons have been learned and identify trends that may lead to a potential reduction in costs and improve patient safety. A Freedom of Information request was made to NHS Resolution for information regarding claims made to otolaryngology departments over the last 10 years. There was a total of 612 successful claims in the 10-year period between 2008/2009 and 2017/2018 with costs of nearly £87 million. Overall, the costs of litigation have increased dramatically, and the main areas for these successful claims can be identified, but restrictions in the detail of information released allows too little insight for improvements to be made to avoid them in future. This continues to be a major problem for healthcare funding and practice.

African swine fever virus evasion of host defences.

African swine fever virus causes a haemorrhagic fever in domestic pigs and wild boar. The continuing spread in Africa, Europe and Asia threatens the global pig industry. The lack of a vaccine limits disease control. To underpin rational strategies for vaccine development improved knowledge is needed of how the virus interacts with and modulates the host's responses to infection. The virus long double-stranded DNA genome codes for more than 160 proteins of which many are non-essential for replication in cells but can have important roles in evading the host's defences. Here we review knowledge of the pathways targeted by ASFV and the mechanisms by which these are inhibited. The impact of deleting single or multiple ASFV genes on virus replication in cells and infection in pigs is summarised providing information on strategies for rational development of modified live vaccines.

Findings from aetiological investigation of Auditory Neuropathy Spectrum Disorder in children referred to cochlear implant programs.

OBJECTIVES: Auditory neuropathy spectrum disorder (ANSD) is an audiological diagnosis characterised by hearing dysfunction in the presence of intact outer hair cell function in the cochlea. ANSD is thought to account for 7-10% of all childhood permanent hearing impairment, and can result from a range of pathological processes. This paper describes the rationale, methods and findings from the aetiological investigation of ANSD. METHODS: Retrospective audit of four cochlear implant programmes. RESULTS: 97 patients were identified. 79% of patients were identified before the age of one. Prematurity and jaundice were the most frequently identified aetiological factors. 33 patients had cochlear nerve deficiency on imaging. Genetic diagnoses identified included otoferlin, SX010 gene, connexin 26 and A1FM1 gene mutations. ANSD was seen in conjunction with syndromes including Kallman syndrome, CHARGE syndrome, X-linked deafness, SOTOS syndrome, Brown Vieletto Van Laere syndrome, and CAPOS syndrome. DISCUSSION: We present a two-level system of aetiological investigation that is clinically practical. Patients with ANSD sufficiently severe to consider cochlear implantation are generally identified at an early age. Aetiological investigation is important to guide prognosis and identify comorbidity. CONCLUSION: Prematurity and jaundice are the most commonly identified aetiological factors in ANSD. Imaging findings identify crucial factors in a significant minority. An important minority may have genetic and syndromic diagnoses that require further management.

Micro magnetic resonance angiography of the finger in systemic sclerosis.

OBJECTIVE: To characterize vascular lesions in SSc disease with high-resolution magnetic resonance angiography (Micro-MRA) of the finger. METHODS: Eight SSc subjects and eight age- and sex-matched healthy controls were recruited for this study. Among the SSc subjects, the mean +/- s.d. age was 54.5 +/- 4.9 yrs, and the mean +/- s.d. duration of disease was 8.3 +/- 8.4 yrs. The numbers of SSc subjects that had telangiectasia, calcinosis and impaired finger flexion were 3, 2 and 3, respectively. The 2D time-of-flight micro-MRA was performed on a 3T clinical MRI scanner using a custom-designed finger coil with an in-plane resolution of 0.16 x 0.21 mm(2) and slice thickness of 1.2 mm. The data for the proper palmar digital artery lumen area, the number of visible dorsal digital veins and a semi-quantitative vascular score, which evaluates the overall integrity of digital vessels, were independently evaluated by two experienced reviewers who were blinded to the status of the subject. RESULTS: Micro-MRA detected significant differences in the digital vasculature between SSc subjects and healthy volunteers. The SSc subjects had a significantly decreased digital artery lumen area (0.13 +/- 0.06 vs 0.53 +/- 0.26 mm(2), P < 0.001), a reduced number of digital veins (0.63 +/- 1.06 vs 3.13 +/- 0.99, P = 0.001) and a lowered overall vascular score (1.75 +/- 1.04 vs 3.5 +/- 0.53, P = 0.001). The study also found that both the digital artery lumen area (Pearson's; r = -0.72, P = 0.044) and vascular scores (Spearman's; rho = -0.75, P = 0.047) of the SSc subjects were inversely correlated with the duration of the disease. CONCLUSIONS: Micro-MRA can be used to identify and quantitatively characterize the vascular disease in SSc fingers. The parameters derived from micro-MRA could potentially be used as prospective biomarkers for clinical evaluation.