Sleep related rhythmic movement disorder: phenotypic characteristics and treatment response in a paediatric cohort.

OBJECTIVE: To describe phenotypic, polysomnographic characteristics, impact, and treatment response in children with sleep related rhythmic movement disorder (SR-RMD). BACKGROUND: There is limited research on SR-RMD. We have developed a systematic clinical evaluation of children with SR-RMD to improve understanding and treatment. METHODS: A retrospective chart review of 66 children at a UK tertiary hospital. Baseline assessment included validated screening questionnaires to study autism spectrum characteristics, general behaviour and sensory profile. A standardised questionnaire assessed impact on sleep quality and daytime wellbeing of child and family. Polysomnography data were collated. RESULTS: Children were aged 0.9-16.3 years (78.8% male). 51.5% had a neurodevelopmental disorder, most commonly autism spectrum disorder. High rates of behavioural disturbance and sensory processing differences were reported, not confined to children with neurodevelopmental disorders. Parents reported concerns about risk of injury, loss of sleep and persistence into adulthood. Daytime wellbeing was affected in 72% of children and 75% of other family members. Only 31/48 children demonstrated rhythmic movements during video-polysomnography, occupying on average 6.1% of time in bed. Most clusters occurred in the settling period but also arose from N1, N2 and REM sleep and wake after sleep onset. Melatonin was prescribed to 52 children, all but one were extended-release preparations. 24/27 children with available data were reported to improve with melatonin. CONCLUSIONS: SR-RMD places a significant burden on child and family wellbeing. Our novel findings of sensory processing differences in this population and parent reported therapeutic response to extended-release melatonin offer potential avenues for future research.

Echocardiographic evaluation of regurgitant fraction in dogs with subclinical myxomatous mitral valve disease: Method comparison, effects of pimobendan, and reproducibility.

INTRODUCTION/OBJECTIVES: To evaluate regurgitant fraction (RF) using Simpson's method of discs to estimate total stroke volume (RFSMOD_TSV) and using Motion-mode to estimate total stroke volume (RFM-modeTSV) in dogs with subclinical myxomatous mitral valve disease (MMVD). We also sought to evaluate the effects of pimobendan on RF, and to determine the reproducibility of RFSMOD_TSV and RFM-modeTSV. ANIMALS, MATERIALS, AND METHODS: Echocardiography was performed on 57 dogs with MMVD (30 stage B1 and 27 stage B2). Ten dogs received pimobendan for 7-10 days and had a second echocardiogram. Nine dogs underwent six repeated echocardiographic examinations by two operators on three nonconsecutive days within one week for reproducibility analysis. RESULTS: Both RFSMOD_TSV and RFM-modeTSV exhibited a curvilinear relationship with left atrium-to-aortic root ratio. Both RFSMOD_TSV and RFM-modeTSV varied considerably within stage B1 (minimum-maximum: -9.1%-58.2% and -35.7%-66.2%, respectively) and B2 (13.6%-76.2% and 20.1%-85.7%, respectively). Method comparison showed RFSMOD_TSV and RFM-modeTSV were not interchangeable with proportional bias. Pimobendan significantly reduced RFSMOD_TSV (-32.0% ± 23.3%) and RFM-modeTSV (-19.2% ± 10.9%) within the same dog and relative to controls. Good inter-day and between-operator reproducibility was observed for RFSMOD_TSV and RFM-modeTSV based on intraclass correlation coefficients 0.86-0.90 and 0.83-0.90, respectively. Reproducibility coefficients were 19.6%-24.1% and 24.1%-27.0%, respectively. CONCLUSIONS: Use of RF using the total stroke volume method to aid the assessment of dogs with subclinical MMVD might be of clinical value. However, further study is warranted. Based on response to pimobendan and reproducibility analysis, RF SMOD_TSV might be a more reliable technique to quantify RF.

The impact of multidisciplinary team decision-making in locally advanced and recurrent rectal cancer.

INTRODUCTION: Appropriate patient selection within the context of a multidisciplinary team (MDT) is key to good clinical outcomes. The current evidence base for factors that guide the decision-making process in locally advanced rectal cancer (LARC) and locally recurrent rectal cancer (LRRC) is limited to anatomical factors. METHODS: A registry-based, prospective cohort study was undertaken of patients referred to our specialist MDT between 2015 and 2019. Data were collected on patients and disease characteristics including performance status, Charlson Comorbidity Index, the English Index of Multiple Deprivation quintiles and MDT treatment decision. Curative treatment was defined as neoadjuvant treatment and surgical resection that would achieve a R0 resection, and/or complete treatment of distant metastatic disease. Palliative treatment was defined as non-surgical treatment. RESULTS: In total, 325 patients were identified; 72.7% of patients with LARC and 63.6% of patients with LRRC were offered treatment with curative intent (p = 0.08). Patients with poor performance status (PS > 2; p < 0.001), severe comorbidity (p < 0.001), socio-economic deprivation (p = 0.004), a positive predictive circumferential resection margin (p = 0.005) and metastatic disease (p < 0.001) were associated with palliative treatment. Overall survival in the curative cohort was 49 months (95% confidence interval [CI] 32.4-65.5) compared with 12 months (95% CI 9.1-14.9) in the palliative cohort (p < 0.001). The presence of metastatic disease was identified as a prognostic factor for patients undergoing curative treatment (p = 0.05). The only prognostic factor identified in patients treated palliatively was performance status (p < 0.001). CONCLUSIONS: Our study identifies a number of preoperative, prognostic factors that affect MDT decision-making and overall survival.

Aorto-left atrial fistula secondary to infective aortic endocarditis and endarteritis in a cat with valvular aortic stenosis.

A cat previously diagnosed with valvular aortic stenosis developed acute respiratory distress. A new continuous heart murmur was noted on physical exam. Echocardiographic examination revealed vegetative lesions on the aortic valve and continuously shunting blood flow from the aorta into the left atrium. Despite initial treatment for left-sided congestive heart failure, the cat died suddenly. In addition to confirming aortic valve endocarditis and an acquired aorto-left atrial shunt, pathological examination identified vegetative lesions on the luminal surface of the ascending aorta. Although antemortem aerobic blood culture, 16s bacterial ribosomal DNA PCR, and Bartonella PCR failed to identify causative organisms, Escherichia coli was identified on postmortem tissue culture of the aortic lesion. This represented a unique case of primary valvular aortic stenosis with secondary infective aortic endocarditis, infective aortic endarteritis, and aorto-left atrial fistula in a cat. It highlighted potential adverse outcomes of aortic stenosis that are more commonly recognized in humans and dogs.

Community intervention for cardiovascular disease risk factors in Kalutara, Sri Lanka.

BACKGROUND: The effectiveness of a 2015-17 community intervention to reduce cardiovascular disease (CVD) and type 2 diabetes (T2DM) risk factors is assessed in a Sri Lanka adult population, using a before-and-after study design. METHODS: Four contiguous Public Health Midwife (PHM) areas in Kalutara district (Western Province) were exposed to a Sri Lankan designed community health promotion initiatives (without screening) to lower CVD and T2DM risk factors. Pre- and post-intervention surveys (2014, n=1,019; 2017, n=908) were of 25-64 year males (M) and females (F) from dissimilar randomly selected clusters (villages or settlements) from PHMs, with probability of selection proportional to population size, followed by household sampling, then individual selection to yield equal-probability samples. Differences in resting blood pressure (BP), fasting plasma glucose (FPG), total cholesterol, body mass index and tobacco smoking, adjusting for cluster sampling, age and socio-economic differences, were examined. RESULTS: Hypertension prevalence declined from 25% to 16% (F) (p<.0001), and 21% to 17% (M). Both mean systolic and diastolic BP declined. T2DM declined from 18% to 13% (F), and 18% to 15% (M), as did mean fasting plasma glucose. Elevated total cholesterol declined from 21% to 15% in women (p=0.003) and mean cholesterol declined. Frequency distributions, medians and means of these continuous CVD risk factors shifted to lower levels, and were mostly statistically significant (p< 0.05). CONCLUSIONS: Community health promotion can lower key CVD and T2DM risk factors. Lowering tobacco consumption in males and obesity remain challenges in Sri Lanka.

A near-peer regional surgical teaching programme designed by medical students, delivered by junior doctors.

BACKGROUND: Near-peer teaching initiatives has been shown to be a highly successful method of improving student learning. There has been little data on surgical teaching initiatives of this kind and little data to show if this improves student confidence in surgical topics. This study was designed to show whether a regional surgical teaching programme, delivered by junior doctors, improves confidence levels of students prior to their final examinations. METHOD: Final year medical students were invited from four hospitals in the Northern deanery of England to participate in a voluntary surgical teaching day. Junior doctors were then recruited to present on various surgical topics based on their own knowledge and experience of finals examinations and working on the wards. A pre and post-course questionnaire was designed, validated and distributed to the students to assess their confidence on a five-point Likert scale of 1-5 (1- most confidence, 5- least confidence) levels in each of the 11 chosen topics. Other variables were also measured relating to the topics including visual material, enthusiasm, content relevance and communication. RESULTS: 53 students completed the questionnaire (n = 53). There were 31 females and 22 males with a mean age of 24.7. A mean level of confidence of 2.7 pre-course and 1.6 post-course showed an increase in confidence by 68.8%. All eleven topics covered showed improvement in confidence. General Surgical Principles showed the lowest improvement in confidence from 2.683 to 1.917 (p = <0.001) compared to endocrine which showed the maximum increased in confidence from 3.650 to 1.694 (p = <0.0001). Orthopedics showed an increased in confidence from 3.010 to 1.62 (p = <0.0001). CONCLUSION: Near-peer education designed by medical students and delivered by junior doctors is an effective way for improving confidence levels and test results prior to finals examination and is also valuable for junior doctors.

PD-L1 and immune infiltrates are differentially expressed in distinct subgroups of gastric cancer.

This study investigates the association of PD-L1 expression and immune cell infiltrates and their impact on clinical outcome, in addition to their overlap with microsatellite instability (MSI), HER2 and ATM molecular subgroups of gastric cancer (GC). PD-L1 membrane expression on tumour cells (TC) and infiltrating immune cells (IC), CD3 + T-lymphocytes, CD8+ cytotoxic T-cells, ATM and HER2 were assessed by immunohistochemistry (IHC) in the ACRG (Asian Cancer Research Group) GC cohort (N = 380). EBV status was determined using in situ hybridization and MSI status was performed using PCR and MLH1 IHC. The PD-L1 segment was associated with increased T-cell infiltrates, while the MSI-high segment was enriched for PD-L1, CD3, and CD8. Multivariate analysis confirmed PD-L1 positivity, high CD3 and high CD8 as independent prognostic factors for both disease-free survival and overall survival (all p < 0.05). Patients with MSI-high tumours had better overall survival by both univariate and multivariate analysis. The ATM-low and HER2-high subgroups differed markedly in their immune profile; the ATM-low subgroups enriched for MSI, PD-L1 positivity and CD8 + T-cells, while the HER2 segment was enriched for MSS, with no enrichment for immune markers. Hence, we demonstrate a molecular profiling approach that can divide GC into four molecular subgroups, namely ATM-low, HER2-high, PD-L1 positive and MSI-high with differing levels of immune infiltrates and prognostic significance which may help to stratify patients for response to targeted therapies.

Testing the photon-number statistics of a quantum key distribution light source.

A commonly held tenet is that lasers well above threshold emit photons in a coherent state, which follow Poissonian statistics when measured in photon number. This feature is often exploited to build quantum-based random number generators or to derive the secure key rate of quantum key distribution systems. Hence the photon number distribution of the light source can directly impact the randomness and the security distilled from such devices. Here, we propose a method based on measuring correlation functions to experimentally characterize a light source's photon statistics and use it in the estimation of a quantum key distribution system's key rate. This promises to be a useful tool for the certification of quantum-related technologies.

The transcriptional landscape of polyploid wheat.

The coordinated expression of highly related homoeologous genes in polyploid species underlies the phenotypes of many of the world's major crops. Here we combine extensive gene expression datasets to produce a comprehensive, genome-wide analysis of homoeolog expression patterns in hexaploid bread wheat. Bias in homoeolog expression varies between tissues, with ~30% of wheat homoeologs showing nonbalanced expression. We found expression asymmetries along wheat chromosomes, with homoeologs showing the largest inter-tissue, inter-cultivar, and coding sequence variation, most often located in high-recombination distal ends of chromosomes. These transcriptionally dynamic genes potentially represent the first steps toward neo- or subfunctionalization of wheat homoeologs. Coexpression networks reveal extensive coordination of homoeologs throughout development and, alongside a detailed expression atlas, provide a framework to target candidate genes underpinning agronomic traits in wheat.

The temperature of storage of a batch of wheat distillers dried grains with solubles samples on their nutritive value for broilers.

1. A batch of wheat distillers dried grains with solubles (DDGS) was obtained immediately after production and was separated into 5 equal parts and placed in woven polypropylene sacks. The samples were stored under 5 different temperature conditions for 1 year as follows: kept at a constant -20°C; kept at -20°C for 24 h period and after that kept at a constant +4°C; kept at a constant +4°C only; kept at a constant +15°C; stored at ambient temperature (range of weekly mean temperatures was from +4 to +22°C). 2. Each of the 5 wheat DDGS samples was included (200 g/kg) in a nutritionally complete diet and fed to broiler chickens from 7 to 21 d of age. The chemical composition of the DDGS samples was determined at the beginning and at the end of the 1-year storage period. 3. The nitrogen corrected apparent metabolisable energy (AMEn) and the nutrient availability of each sample was measured using a total collection technique. The growth performance of birds was also determined. 4. The DDGS samples kept at a constant -20°C had higher dry matter, lower oxidation value and lower antioxidant contents. The DDGS sample that was stored at ambient temperatures had a higher AMEn than the rest of the DDGS samples. 5. The results of this experiment have shown that there can be changes in the AMEn of wheat DDGS during storage at ambient temperatures. In general, there were no serious effects of storage of DDGS on its feeding value to broiler chickens.

Correction to: Abstracts : 29th European Congress of Pathology.

Due to an error with the registration system, the following abstract was regrettably omitted from the Poster Sessions. The abstract should have been included as PS-10-021 and displayed on page S166.

Experimental measurement-device-independent quantum digital signatures.

The development of quantum networks will be paramount towards practical and secure telecommunications. These networks will need to sign and distribute information between many parties with information-theoretic security, requiring both quantum digital signatures (QDS) and quantum key distribution (QKD). Here, we introduce and experimentally realise a quantum network architecture, where the nodes are fully connected using a minimum amount of physical links. The central node of the network can act either as a totally untrusted relay, connecting the end users via the recently introduced measurement-device-independent (MDI)-QKD, or as a trusted recipient directly communicating with the end users via QKD. Using this network, we perform a proof-of-principle demonstration of QDS mediated by MDI-QKD. For that, we devised an efficient protocol to distil multiple signatures from the same block of data, thus reducing the statistical fluctuations in the sample and greatly enhancing the final QDS rate in the finite-size scenario.

Oncological and quality of life outcomes following extralevator versus standard abdominoperineal excision for rectal cancer.

INTRODUCTION There is increasing and conflicting research debating the oncological benefits of extralevator abdominoperineal excision (ELAPE) compared with standard abdominoperineal excision (SAPE). However, there is very little in the literature on the long-term effects on patients' wellbeing following the two procedures. The aim of this study was to determine the oncological outcomes and long-term quality of life (QoL) of patients at two hospitals having undergone ELAPE or SAPE. METHODS Consecutive patients with rectal cancer who underwent either ELAPE or SAPE between January 2009 and June 2015 at a single centre were analysed. Oncological outcomes were determined by histology and follow-up imaging. QoL data were obtained prospectively using the QLQ-C30 and QLQ-CR29 questionnaires. RESULTS A total of 48 patients (36 male, 12 female; 27 ELAPE, 21 SAPE) were reviewed. The mean age was 67.4 years and the median follow-up duration was 44 months (range: 6-79 months). Four patients (2 ELAPE, 2 SAPE) developed local recurrence. Rates of distant metastasis were similar (ELAPE: 11%, SAPE: 14%). There was no significant difference in mean global health status score (ELAPE: 77.3, SAPE: 65.3). Impotence was the most frequently reported problem (mean symptom scores of 89.7 and 78.8 for ELAPE and SAPE respectively). CONCLUSIONS This is the largest study with the longest follow-up period that compares QoL after ELAPE with that after SAPE. Although more radical in nature, ELAPE did not demonstrate any significant impact on QoL compared with SAPE. There was no significant difference in long-term oncological outcome between the groups. Impotence remains a significant problem for all patients and they should be well informed of this risk prior to surgery.

Quantum key distribution with hacking countermeasures and long term field trial.

Quantum key distribution's (QKD's) central and unique claim is information theoretic security. However there is an increasing understanding that the security of a QKD system relies not only on theoretical security proofs, but also on how closely the physical system matches the theoretical models and prevents attacks due to discrepancies. These side channel or hacking attacks exploit physical devices which do not necessarily behave precisely as the theory expects. As such there is a need for QKD systems to be demonstrated to provide security both in the theoretical and physical implementation. We report here a QKD system designed with this goal in mind, providing a more resilient target against possible hacking attacks including Trojan horse, detector blinding, phase randomisation and photon number splitting attacks. The QKD system was installed into a 45 km link of a metropolitan telecom network for a 2.5 month period, during which time the system operated continuously and distributed 1.33 Tbits of secure key data with a stable secure key rate over 200 kbit/s. In addition security is demonstrated against coherent attacks that are more general than the collective class of attacks usually considered.

Transcript analysis in two alfalfa salt tolerance selected breeding populations relative to a non-tolerant population.

With the growing limitations on arable land, alfalfa (a widely cultivated, low-input forage) is now being selected to extend cultivation into saline lands for low-cost biofeedstock purposes. Here, minerals and transcriptome profiles were compared between two new salinity-tolerant North American alfalfa breeding populations and a more salinity-sensitive western Canadian alfalfa population grown under hydroponic saline conditions. All three populations accumulated two-fold higher sodium in roots than shoots as a function of increased electrical conductivity. At least 50% of differentially expressed genes (p < 0.05) were down-regulated in the salt-sensitive population growing under high salinity, while expression remained unchanged in the saline-tolerant populations. In particular, most reduction in transcript levels in the salt-sensitive population was observed in genes specifying cell wall structural components, lipids, secondary metabolism, auxin and ethylene hormones, development, transport, signalling, heat shock, proteolysis, pathogenesis-response, abiotic stress, RNA processing, and protein metabolism. Transcript diversity for transcription factors, protein modification, and protein degradation genes was also more strongly affected in salt-tolerant CW064027 than in salt-tolerant Bridgeview and salt-sensitive Rangelander, while both saline-tolerant populations showed more substantial up-regulation in redox-related genes and B-ZIP transcripts. The report highlights the first use of bulked genotypes as replicated samples to compare the transcriptomes of obligate out-cross breeding populations in alfalfa.

Quantitative structure-property relationships for predicting sorption of pharmaceuticals to sewage sludge during waste water treatment processes.

Understanding the sorption of pharmaceuticals to sewage sludge during waste water treatment processes is important for understanding their environmental fate and in risk assessments. The degree of sorption is defined by the sludge/water partition coefficient (Kd). Experimental Kd values (n=297) for active pharmaceutical ingredients (n=148) in primary and activated sludge were collected from literature. The compounds were classified by their charge at pH7.4 (44 uncharged, 60 positively and 28 negatively charged, and 16 zwitterions). Univariate models relating log Kd to log Kow for each charge class showed weak correlations (maximum R2=0.51 for positively charged) with no overall correlation for the combined dataset (R2=0.04). Weaker correlations were found when relating log Kd to log Dow. Three sets of molecular descriptors (Molecular Operating Environment, VolSurf and ParaSurf) encoding a range of physico-chemical properties were used to derive multivariate models using stepwise regression, partial least squares and Bayesian artificial neural networks (ANN). The best predictive performance was obtained with ANN, with R2=0.62-0.69 for these descriptors using the complete dataset. Use of more complex Vsurf and ParaSurf descriptors showed little improvement over Molecular Operating Environment descriptors. The most influential descriptors in the ANN models, identified by automatic relevance determination, highlighted the importance of hydrophobicity, charge and molecular shape effects in these sorbate-sorbent interactions. The heterogeneous nature of the different sewage sludges used to measure Kd limited the predictability of sorption from physico-chemical properties of the pharmaceuticals alone. Standardization of test materials for the measurement of Kd would improve comparability of data from different studies, in the long-term leading to better quality environmental risk assessments.

HBA score in relation to donor semen profiles and live birth rates: a preliminary study.

We sought to determine whether sperm donor selection could be improved by using the hyaluronan binding assay (HBA) score to predict live birth rates (LBRs) in donor insemination treatments. Thirty donor samples were included: five fresh samples to assess whether HBA score is affected by cryopreservation and 25 frozen samples from donors whose sperm gave rise to known live births, divided into three groups, with success rates ≥50%, <50-33% and <33%, to examine whether HBA score correlates with LBRs. Correlations with semen analysis parameters, as well as donor demographic factors, known causes of patient subfertility and/or the type of treatment provided were also assessed. There was no significant difference in the mean HBA score pre- and post-cryopreservation (p = 0.998) nor in the HBA score of the three different outcome groups (p = 0.89). HBA score was not significantly affected by other semen analysis parameters (r2=0.394, p = 0.127) or any of the other examined factors. This was the first study to investigate HBA score for cryopreserved donor samples with known LBRs. HBA score was not correlated with LBRs in this small pilot study. Larger studies are required to validate HBA score as a tool for sperm donor selection and predictor of LBRs.

Quantum key distribution over multicore fiber.

We present the first quantum key distribution (QKD) experiment over multicore fiber. With space division multiplexing, we demonstrate that weak QKD signals can coexist with classical data signals launched at full power in a 53 km 7-core fiber, while showing negligible degradation in performance. Based on a characterization of intercore crosstalk, we perform additional simulations highlighting that classical data bandwidths beyond 1Tb/s can be supported with high speed QKD on the same fiber.

Non-functioning parathyroid adenoma: a rare differential diagnosis for vocal-cord paralysis.

Introduction Adenomas of the parathyroid gland typically present with symptoms of hyperparathyroidism, manifested by fatigue, bone pain, abdominal pain, weakness, dyspepsia, nephrolithiasis and skeletal bone disease. Here, we describe, for the first time, a case of a non-functioning benign tumour of the parathyroid gland presenting as vocal-cord paralysis. Case History A 49-year-old male presented with a 10-week history of dysphonia and the feeling of having 'something stuck in my throat'. History-taking elicited no other associated symptoms. Flexible nasal endoscopy demonstrated paralysis of the left vocal cord. Computed tomography of the neck revealed a cystic lesion, 18mm in diameter adjacent to the oesophagus. After more rigorous tests, a neck exploration, left hemithyroidectomy, excision of the left paratracheal mass and level-VI neck dissection was undertaken, without incident to the patient or surgical team. Histology was consistent with a parathyroid adenoma. Conclusions This case emphasises the importance of including adenomatous disease of the parathyroid gland in the differential diagnosis despite normal parathyroid status as a cause of vocal cord palsy.

Highly Flexible Silicone Coated Neural Array for Intracochlear Electrical Stimulation.

We present an effective method for tailoring the flexibility of a commercial thin-film polymer electrode array for intracochlear electrical stimulation. Using a pneumatically driven dispensing system, an average 232 ± 64 µm (mean ± SD) thickness layer of silicone adhesive coating was applied to stiffen the underside of polyimide multisite arrays. Additional silicone was applied to the tip to protect neural tissue during insertion and along the array to improve surgical handling. Each array supported 20 platinum sites (180 µm dia., 250 µm pitch), spanning nearly 28 mm in length and 400 µm in width. We report an average intracochlear stimulating current threshold of 170 ± 93 µA to evoke an auditory brainstem response in 7 acutely deafened felines. A total of 10 arrays were each inserted through a round window approach into the cochlea's basal turn of eight felines with one delamination occurring upon insertion (preliminary results of the in vivo data presented at the 48th Annual Meeting American Neurotology Society, Orlando, FL, April 2013, and reported in Van Beek-King 2014). Using microcomputed tomography imaging (50 µm resolution), distances ranging from 100 to 565 µm from the cochlea's central modiolus were measured. Our method combines the utility of readily available commercial devices with a straightforward postprocessing step on the order of 24 hours.