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To compare round window niche visibility as seen endoscopically during cochlear implant surgery with pre-operative high-resolution computed tomography of the temporal bone.
Nineteen patients scheduled for cochlear implantation, aged 2–20 years, were referred for computed tomography from October 2016 to March 2018. Angles were measured between the lines passing through the mid-sagittal plane and cochlear basal turn on the scans. Endoscopic round window niche visibility during posterior tympanotomy was categorised as: type I = 100 per cent, type IIa = more than 50 per cent, type IIb = less than 50 per cent or type III = 0 per cent. Pre-operative computed tomography measurements were used to predict round window niche visibility before surgery and correlated with intra-operative findings.
The mean (range) of pre-operative angles on computed tomography for endoscopic visibility types I, IIa and IIb, were 64.06° (61.16–69.37°), 63.81° (58.61–71.35°) and 56.48° (50.37–59.05°), respectively, a statistically significant finding (one-way analysis of variance test, p = 0.016).
Pre-operative high-resolution temporal bone computed tomography measurements are useful in predicting round window niche visualisation as viewed endoscopically during posterior tympanotomy. The angle was more acute in type IIb compared to type I.
Background: Biallelic variants in POLR1C are associated with POLR3-related leukodystrophy (POLR3-HLD), or 4H leukodystrophy (Hypomyelination, Hypodontia, Hypogonadotropic Hypogonadism), and Treacher Collins syndrome (TCS). The clinical spectrum of POLR3-HLD caused by variants in this gene has not been described. Methods: A cross-sectional observational study involving 25 centers worldwide was conducted between 2016 and 2018. The clinical, radiologic and molecular features of 23 unreported and previously reported cases of POLR3-HLD caused by POLR1C variants were reviewed. Results: Most participants presented between birth and age 6 years with motor difficulties. Neurological deterioration was seen during childhood, suggesting a more severe phenotype than previously described. The dental, ocular and endocrine features often seen in POLR3-HLD were not invariably present. Five patients (22%) had a combination of hypomyelinating leukodystrophy and abnormal craniofacial development, including one individual with clear TCS features. Several cases did not exhibit all the typical radiologic characteristics of POLR3-HLD. A total of 29 different pathogenic variants in POLR1C were identified, including 13 new disease-causing variants. Conclusions: Based on the largest cohort of patients to date, these results suggest novel characteristics of POLR1C-related disorder, with a spectrum of clinical involvement characterized by hypomyelinating leukodystrophy with or without abnormal craniofacial development reminiscent of TCS.
Background: Continuous electroencephalographic (cEEG) monitoring is essential to diagnosing non-convulsive seizures (NCS), reported to occur in 7-46% of at-risk critically ill patients. However, cEEG is labour-intensive, and given scarcity of resources at most centres cEEG is feasible in only selected patients. We aim to evaluate the clinical utility of cEEG at our centre in order to optimize further cEEG allocation among critically ill patients. Methods: Using a clinical database, we identified critically ill children who underwent cEEG monitoring in 2016, 2017 and 2018. We abstracted underlying diagnoses, indication for cEEG monitoring, cEEG findings, and associated changes in management. Results: Over this three year period, 928 cEEGs were performed. Among the 100 studies analyzed to date, primary indications for monitoring were characterization of events of unclear etiology (32%), diagnosis of NCS (30%), and monitoring of therapy for seizures (17%). Seizures were captured in 31% of patients (22% subclinical only, 5% electroclinical only, 4% both), which resulted in a treatment change in 90% of cases. Non-epileptic events were captured in 26% of patients. Conclusions: cEEG yielded clinically meaningful information in 57% of cases, frequently resulting in management changes. Subgroup analyses by cEEG indication and ICU location will be presented.
To propose a new classification of inner-ear anomalies that is more clinically oriented and surgically relevant: the SMS (Sawai Man Singh) classification of cochleovestibular malformations.
A retrospective multicentric study was conducted of 436 cochlear implantations carried out in 3 Indian tertiary care institutes. Patients with anomalous anatomy were included and classified, as per the new SMS classification, into cochleovestibular malformation types I, II, III and IV, based on cochlear morphology, modiolus and lamina cribrosa.
There were 19, 23, 8 and 4 patients with cochleovestibular malformation types I, II, III and IV, respectively. Two-year post-operative Meaningful Auditory Integration Scale scores were statistically analysed.
This new classification for inner-ear anomalies is a simpler, more practical, outcome-oriented classification that can be used to better plan the surgery. These merits make it a more uniform classification for recording results.
Obstructive sleep apnoea is a common chronic sleep disorder characterised by collapse of the upper airway during sleep. The nasal airway forms a significant part of the upper airway and any obstruction is thought to have an impact on obstructive sleep apnoea. A systematic review was performed to determine the role of rhinological surgical interventions in the management of obstructive sleep apnoea.
A systematic review of current literature was undertaken; studies were included if they involved comparison of a non-surgical and/or non-rhinological surgical intervention with a rhinological surgical intervention for treatment of obstructive sleep apnoea.
Sixteen studies met the selection criteria. The pooled data suggest that there are reductions in the apnoea/hypopnea index and respiratory disturbance index following nasal surgery. However, the current body of studies is too heterogeneous for statistically significant meta-analysis to be conducted.
Nasal surgery may have limited benefit for a subset of patients based on current evidence.
Rice has the lowest grain protein content (GPC) among cereals. Efforts have been made to improve GPC through the modified bulk-pedigree method of selection. A total of 1780 F8 recombinant lines were derived in the year 2013 from five different cross combinations involving two high-GPC landraces, namely ARC10075 and ARC10063, three high-yielding parents, namely Swarna, Naveen and IR64, and one parent, namely Sharbati, known for superior grain quality with high micronutrient content. Near-infrared spectroscopy was used to facilitate high-throughput selection for GPC. Significant selection differential, response to selection and non-significant differences between the predicted and observed response to selection for GPC and protein yield indicated the effectiveness of this selection process. This resulted in lines with high GPC, protein yield and desirable levels of amylose content. Further, based on high mean and stability for GPC and protein yield over the environments in the wet seasons of 2013, 2014 and the dry season of 2014, 12 elite lines were identified. Higher accumulation of glutelin fraction and non-significant change in prolamin/glutelin ratio in the grain suggested safe guarding of the nutritional value of rice grain protein of most of these identified lines. Since rice is the staple food of millions, the output of breeding for high GPC could have a significant role in alleviating protein malnutrition, especially in the developing world.
There is lack of evidence on the differential impact of maternal macronutrient consumption: carbohydrates (CHO), fats and protein on birth weight. We investigated the association between maternal dietary macronutrient intakes and their sub-components such as saccharides and fatty acids and birth weight. This analyses included 1,196 women with singleton pregnancies who were part of the CAffeine and REproductive health study in Leeds, UK between 2003 and 2006. Women were interviewed in each trimester. Dietary information was collected twice using a 24-h dietary recall about 8–12 weeks and 13–27 weeks of gestation. Multiple linear regression models adjusted for alcohol and smoking in trimester 1, showed that each additional 10 g/d CHO consumption was associated with an increase of 4 g (95 % CI 1, 7; P=0·003) in birth weight. Conversely, an additional 10 g/d fat intake was associated with a lower birth weight of 8 g (95 % CI 0, 16; P=0·04) when we accounted for energy contributing macronutrients in each model, and maternal height, weight, parity, ethnicity, gestational age at delivery and sex of the baby. There was no evidence of an association between protein intake and birth weight. Maternal diet in trimester 2 suggested that higher intakes of glucose (10 g/d) and lactose (1 g/d) were both associated with higher birth weight of 52 g (95 % CI 4, 100; P=0·03) and 5 g (95 % CI 2, 7; P<0·001) respectively. These results show that dietary macronutrient composition during pregnancy is associated with birth weight outcomes. An appropriately balanced intake of dietary CHO and fat during pregnancy could support optimum birth weight.
The Global Muon Detector Network (GMDN) is composed by four ground cosmic ray detectors distributed around the Earth: Nagoya (Japan), Hobart (Australia), Sao Martinho da Serra (Brazil) and Kuwait city (Kuwait). The network has operated since March 2006. It has been upgraded a few times, increasing its detection area. Each detector is sensitive to muons produced by the interactions of ~50 GeV Galactic Cosmic Rays (GCR) with the Earth′s atmosphere. At these energies, GCR are known to be affected by interplanetary disturbances in the vicinity of the earth. Of special interest are the interplanetary counterparts of coronal mass ejections (ICMEs) and their driven shocks because they are known to be the main origins of geomagnetic storms. It has been observed that these ICMEs produce changes in the cosmic ray gradient, which can be measured by GMDN observations. In terms of applications for space weather, some attempts have been made to use GMDN for forecasting ICME arrival at the earth with lead times of the order of few hours. Scientific space weather studies benefit the most from the GMDN network. As an example, studies have been able to determine ICME orientation at the earth using cosmic ray gradient. Such determinations are of crucial importance for southward interplanetary magnetic field estimates, as well as ICME rotation.
In low- and middle-income countries, mental health training often includes sending few generalist clinicians to specialist-led programs for several weeks. Our objective is to develop and test a video-assisted training model addressing the shortcomings of traditional programs that affect scalability: failing to train all clinicians, disrupting clinical services, and depending on specialists.
We implemented the program -video lectures and on-site skills training- for all clinicians at a rural Nepali hospital. We used Wilcoxon signed-rank tests to evaluate pre- and post-test change in knowledge (diagnostic criteria, differential diagnosis, and appropriate treatment). We used a series of ‘Yes’ or ‘No’ questions to assess attitudes about mental illness, and utilized exact McNemar's test to analyze the proportions of participants who held a specific belief before and after the training. We assessed acceptability and feasibility through key informant interviews and structured feedback.
For each topic except depression, there was a statistically significant increase (Δ) in median scores on knowledge questionnaires: Acute Stress Reaction (Δ = 20, p = 0.03), Depression (Δ = 11, p = 0.12), Grief (Δ = 40, p < 0.01), Psychosis (Δ = 22, p = 0.01), and post-traumatic stress disorder (Δ = 20, p = 0.01). The training received high ratings; key informants shared examples and views about the training's positive impact and complementary nature of the program's components.
Video lectures and on-site skills training can address the limitations of a conventional training model while being acceptable, feasible, and impactful toward improving knowledge and attitudes of the participants.
To investigate the feasibility of a national audit of epistaxis management led and delivered by a multi-region trainee collaborative using a web-based interface to capture patient data.
Six trainee collaboratives across England nominated one site each and worked together to carry out this pilot. An encrypted data capture tool was adapted and installed within the infrastructure of a university secure server. Site-lead feedback was assessed through questionnaires.
Sixty-three patients with epistaxis were admitted over a two-week period. Site leads reported an average of 5 minutes to complete questionnaires and described the tool as easy to use. Data quality was high, with little missing data. Site-lead feedback showed high satisfaction ratings for the project (mean, 4.83 out of 5).
This pilot showed that trainee collaboratives can work together to deliver an audit using an encrypted data capture tool cost-effectively, whilst maintaining the highest levels of data quality.
Goats make up the largest group of ruminant livestock in Nigeria and are strategic in bridging animal protein supply gap and improving the economy of rural households. The hypervariable region 1 (HVR1) of the caprine mitochondrial genome was investigated to better understand genetic diversity important for improving selection for animal breeding and conservation programs. We sequenced and analysed the mitochondrial DNA (mtDNA) HVR1 in 291 unrelated indigenous Nigerian goats (West African Dwarf (WAD), Red Sokoto (RSO) and Sahel (SAH)), randomly sampled from around the country, and compared them with the HVR1 sequences of 336 Indian goats and 12 other sequences in five different species in the genus Capra (C. falconeri, C. ibex nubiana, C. aegagrus, C. cylindricornis and C. sibirica). A total of 139 polymorphic sites from 291 individuals were captured in 204 haplotypes. Within and among population variations were 77.25 and 22.74 percent, respectively. Nigerian goats showed high genetic diversity (0.87) and high FST values, and separate from Indian goats and other wild species. Haplogroups in WAD separates it from RSO and SAH concomitant with a different demographic history. Clear genetic structure was found among Nigerian goat breeds with appreciable variation in mtDNA HVR1 region. This study grouped Nigerian goat breeds into two major groups suggesting two different demographic origins for Northern and Southern breeds. High genetic admixing denotes different maternal origins and in contrast to evidence from goats from Levant and Central Asia, where goats were originally domesticated.
Lower and middle income countries (LMICs) are home to >80% of the global population, but mental health researchers and LMIC investigator led publications are concentrated in 10% of LMICs. Increasing research and research outputs, such as in the form of peer reviewed publications, require increased capacity building (CB) opportunities in LMICs. The National Institute of Mental Health (NIMH) initiative, Collaborative Hubs for International Research on Mental Health reaches across five regional ‘hubs’ established in LMICs, to provide training and support for emerging researchers through hub-specific CB activities. This paper describes the range of CB activities, the process of monitoring, and the early outcomes of CB activities conducted by the five research hubs.
The indicators used to describe the nature, the monitoring, and the early outcomes of CB activities were developed collectively by the members of an inter-hub CB workgroup representing all five hubs. These indicators included but were not limited to courses, publications, and grants.
Results for all indicators demonstrate a wide range of feasible CB activities. The five hubs were successful in providing at least one and the majority several courses; 13 CB recipient-led articles were accepted for publication; and nine grant applications were successful.
The hubs were successful in providing CB recipients with a wide range of CB activities. The challenge remains to ensure ongoing CB of mental health researchers in LMICs, and in particular, to sustain the CB efforts of the five hubs after the termination of NIMH funding.
The spatial peaks QRS-T angle accurately distinguishes children with hypertrophic cardiomyopathy from their healthy counterparts. The spatial peaks QRS-T angle is also useful in risk stratification for ventricular arrhythmias. We hypothesised that the spatial peaks QRS-T angle would be useful for the prediction of ventricular arrhythmias in hypertrophic cardiomyopathy patients under 23 years of age.
Corrected QT interval and spatial peaks QRS-T angles were retrospectively assessed in 133 paediatric hypertrophic cardiomyopathy patients (12.4±6.6 years) with versus without ventricular arrhythmias of 30 seconds or longer. Significance, positive/negative predictive values, and odds ratios were calculated based on receiver operating characteristic curve cut-off values.
In total, 10 patients with ventricular arrhythmias were identified. Although the corrected QT interval did not differentiate those with versus without ventricular arrhythmias, the spatial peaks QRS-T angle did (151.4±19.0 versus 116.8±42.6 degrees, respectively, p<0.001). At an optimal cut-off value (124.1 degrees), the positive and negative predictive values of the spatial peaks QRS-T angle were 15.4 and 100.0%, respectively, with an odds ratio of 25.9 (95% CI 1.5–452.2).
In children with hypertrophic cardiomyopathy, the spatial peaks QRS-T angle is associated with ventricular arrhythmia burden with high negative predictive value and odds ratio.
Background: NMDA receptor encephalitis (NMDARE) is associated with pre-existing psychiatric symptoms and seizure disorders. It is not typically associated with elevated ICP. Diagnostically, EEG findings in NMDARE are characteristic as are the pathological features of ovarian teratomas associated with this disease. We report a patient who tested positive for NMDARE however presented with features not known to be associated with the disease including elevated ICP, atypical EEG findings and grossly atypical features on pathological section. Results: A 26 year old woman presented with psychiatric symptoms and status epilepticus. On examination, she was found to have papilledema and eleveated ICP on measurement. Her imaging and EEG demonstrated atypical findings, not consistent with NMDARE. CT scan of the abdomen demonstrated an adnexal mass. CSF studies eventually tested positive for NMDARE and following removal of her ovarian teratoma, the pathology demonstrated atypical findings for lesions associated with NMDARE classically. Conclusions: NMDARE is a new entity, which has historically shown a typical clinical course. Our case demonstrates a previously undescribed presentation of NMDARE with elevated ICP, atypical EEG findings and unique pathology of the associated ovarian teratoma.
This study aimed to measure changes in disease-specific quality of life in children following tonsillectomy or adenotonsillectomy.
A multicentre prospective cohort study was performed involving seven ENT departments in England. A total of 276 children entered the study over a 2-month period: 107 underwent tonsillectomy and 128 adenotonsillectomy. Forty-one children referred with throat problems initially managed by watchful waiting were also recruited. The follow-up period was 12 months. Outcome measures were the T14, parental impressions of their child's quality of life and the number of days absent from school.
One-year follow-up data were obtained from 150 patients (52 per cent). The mean baseline T14 score in the non-surgical group was significantly lower (T14 = 23) than in the tonsillectomy group (T14 = 31) or the adenotonsillectomy group (T14 = 35; p < 0.001). There was a significant improvement in the T14 scores of responders in all groups at follow up. The effect size was 1.3 standard deviations (SD) for the non-surgical group, 2.1 SD for the tonsillectomy group and 1.9 SD for the adenotonsillectomy group. Between-group differences did not reach statistical significance. A third of children in the non-surgical group underwent surgery during the follow-up period.
Children who underwent surgical intervention achieved a significant improvement in disease-specific quality of life. Less severely affected children were managed conservatively and also improved over 12 months, but 1 in 3 crossed over to surgical intervention.
To observe the impact of internal mammary node irradiation (IMNI) on disease-free survival (DFS) and overall survival (OS) in postmastectomy women with breast cancer.
Materials and methods
Between 1978 and 1996, 153 women with stage II–III breast cancer were treated with postmastectomy radiation therapy (RT) with IMNI. Their clinical, pathological and treatment characteristics were matched with 166 patients without IMNI. The RT dose was 35 Gy to the chest wall and 40 Gy to the supraclavicular fossa and IMN in 15 fractions over 3 weeks with photons. All patients were planned with two-dimensional technique. Adjuvant chemotherapy was administered to 41% and endocrine therapy to 52% of the patients. Symptomatic patients were further assessed for late pulmonary and late cardiac effects.
The median follow-up period was 203 months (range, 182–224), and the median age was 44 years (range 20–73 years). The IMNI group had significantly more right-sided and inner/central quadrant tumours. Other characteristics were comparable between both the groups. DFS at 15 years with and without IMNI was 64 and 49%, respectively (p=0·0001). On multivariate analysis, IMNI was an independent, positive predictor of DFS [hazard ratio (HR), 2·89; p=0·0001]. Benefit of IMNI on DFS was more apparent in inner/central tumours [HR, 1·48; 95% confidence interval (CI), 1·02–2·88], N2–N3 patients (HR, 1·44; 95% CI, 1·09–2·10) and in those who received chemotherapy (HR, 1·70; 95% CI, 1·07–2·71). OS at 15 years with and without IMNI was 68 and 54%, respectively (p=0·0001). Late pulmonary toxicity was 1·5 versus 1% with and without IMNI, respectively. Late cardiac toxicity was 2·6 versus 1·8% with and without IMNI, respectively.
IMNI significantly improved DFS and OS in postmastectomy breast cancer patients. Benefit of IMNI was seen in patients with central/inner tumours and N2–N3 disease. Late cardiopulmonary toxicities were comparable between the two groups.
This paper addresses the problem of designing low-order and linear robust feedback controllers that provide a priori guarantees with respect to stability and performance when applied to a fluid flow. This is challenging, since whilst many flows are governed by a set of nonlinear, partial differential–algebraic equations (the Navier–Stokes equations), the majority of established control system design assumes models of much greater simplicity, in that they are: firstly, linear; secondly, described by ordinary differential equations (ODEs); and thirdly, finite-dimensional. With this in mind, we present a set of techniques that enables the disparity between such models and the underlying flow system to be quantified in a fashion that informs the subsequent design of feedback flow controllers, specifically those based on the
loop-shaping approach. Highlights include the application of a model refinement technique as a means of obtaining low-order models with an associated bound that quantifies the closed-loop degradation incurred by using such finite-dimensional approximations of the underlying flow. In addition, we demonstrate how the influence of the nonlinearity of the flow can be attenuated by a linear feedback controller that employs high loop gain over a select frequency range, and offer an explanation for this in terms of Landahl’s theory of sheared turbulence. To illustrate the application of these techniques, an
loop-shaping controller is designed and applied to the problem of reducing perturbation wall shear stress in plane channel flow. Direct numerical simulation (DNS) results demonstrate robust attenuation of the perturbation shear stresses across a wide range of Reynolds numbers with a single linear controller.