Neural changes after training with transcranial direct current stimulation to increase speech fluency in adults who stutter

In a randomised controlled trial, we showed that a five-day intervention combining anodal transcranial direct current stimulation over the left inferior frontal cortex with temporary speech fluency enhancing techniques reduces stuttering. Speech fluency was unchanged by the fluency training alone, as predicted. Here, we report the neural changes associated with the intervention, measured using functional MRI during sentence reading before the training and one-week later. We obtained imaging data in 25 adult men who stutter (median age = 32 y, inter-quartile range = 11) at the pre-intervention baseline and again one-week post-intervention. A control group of 15 adult men who do not stutter (median age = 30 y, inter-quartile range = 10) and did not complete the intervention were scanned on one occasion. In a whole-brain analysis of perceptibly fluent sentence reading, we compared the change in task-evoked neural activity in the sub-group of men who stutter who had received active stimulation during the intervention (N=13) with those who had sham stimulation (N=12). We hypothesised that the combination of anodal stimulation over the left inferior frontal cortex and fluency-enhancing training would result in lasting change to the brain networks supporting fluent speech production. An additional region-of-interest analysis explored effects on basal ganglia nuclei, which are thought to have a key role in the casual mechanism of stuttering, and which we hypothesised would be engaged by the behavioural approach used during training (choral and metronome-timed speaking). One week after the intervention, the group who had received active transcranial stimulation showed increased activity in speech-related brain regions, relative to the group who had received sham stimulation. Cortically, these changes were evident in left inferior frontal cortex (pars opercularis and orbitalis), anterior insula, anterior superior temporal gyrus, anterior cingulate cortex, and supplementary motor area. Subcortically, activation increased in the caudate nuclei and putamen bilaterally, and in right globus pallidus and thalamus. Together these regions form cortico-striatal-thalamo-cortical loops involved in the planning and initiation and control of speech movements.Our findings reveal that the mechanism of action of the tDCS intervention involved increasing activity across the network involved in the production of fluent speech, indicating that tDCS can be used to promote neural plasticity to strengthen networks supporting natural fluency. This study advances the potential of using non-invasive brain stimulation to improve therapy efficacy for those people who stutter who choose to work on increasing fluency.

Prone positioning in non-intubated patients with coronavirus – A single-centre experience in Hong Kong

Introduction: Significant ventilator-associated pneumonia and mortality were found in COVID-19 patients who required mechanical ventilation which calls for non-invasive means in managing respiratory failure. Methods: We retrospectively reviewed patients admitted to the intensive care unit of Pamela Youde Nethersole Eastern Hospital in Hong Kong with severe acute respiratory syndrome coronavirus 2 infection from 28 November to 15 December 2020. Patients’ laboratory, respiratory parameters and outcome data were recorded and analysed. Results: Eleven received prone ventilation. The median age was 67 (inter-quartile range: 59–72) years, and median COVID-19 GRAM score was 151 (inter-quartile range: 133–181), representing a high-risk group. There were significant improvements 1 h after awake proning in SpO2 (95% vs 92%, p = 0.008), FiO2 (0.4 vs 0.5, p = 0.003), SpO2/FiO2 (240 vs 184, p = 0.005), respiratory rate (19 vs 26, p = 0.006) and respiratory rate – oxygenation index (13.22 vs 7.67, p = 0.003; Table 1). Although not reaching statistical significance, the median PaO2, PaCO2 and PaO2/FiO2 improved after proning. The overall intubation rate was 22% and intensive care unit mortality was 22%, which is in contrast to 65.5% and 27.6%, respectively, in the first three waves. Although did not reach statistical significance, those received prone ventilation tend to have a lower ICU mortality (9.1% vs 42.9%, p = 0.245) and hospital mortality (18.2% vs 42.9%, p = 0.326). Conclusion: Awake proning potentially minimizes complications from invasive ventilation and provides a low-cost low-risk treatment option in COVID-19 patients with respiratory failure. This is particularly important when healthcare resources are strained at times of a pandemic.

Existence of Similar Leptospira Serovars among Dog Keepers and Their Respective Dogs in Mwanza, Tanzania, the Need for a One Health Approach to Control Measures

This study investigated seroepidemiology of Leptospira serovars among the dog keepers and their dogs in the city of Mwanza, Tanzania. A total of 205 dog keepers and 414 dogs were tested for Leptospira antibodies using a microscopic agglutination test (MAT). The median age of the dog keepers was 26 (inter quartile range (IQR): 17–40) years and median duration of keeping dogs was 36 (IQR: 24–120) months. The seropositivity of Leptospira antibodies was (33/205 (16.1%, 95% CI: 11.0–21.1) among dog keepers and (66/414 (15.9%, 95% CI: 12.4–19.4) among dogs, p = 0.4745. Among the serovars tested (Sokoine, Grippotyphosa, Kenya, Pomona and Hebdomadis), the most prevalent serovar was Sokoine in both dog keepers and their dogs (93.9% (31/33) vs. and 65.1% (43/66), p = 0.009). Thirty-one out of thirty-three seropositive dog keepers (93.9%) had dogs positive for Leptospira antibodies with 28 (84.9%) having similar serovars with their respective seropositive dogs. Having tertiary education (AOR: 0.24, 95% CI: 0.07–0.84, p = 0.026) independently protected individuals from being Leptospira seropositive. More than three quarters of dog keepers had similar serovars as their dogs, necessitating one health approach to control measures in endemic areas.

The effect of a traditional and a stick gang-line on the body position of working sled dogs

This study aimed to investigate the effect of two different gang-lines on the pulling angle of sled dogs. It was hypothesised that dogs would run with a straighter angle of pull (in relation to the main-line) in stick gang-lines (STICK) than they would do in traditional gang-lines (TRAD). Eight sled dogs, divided into two teams, ran a 3.1 km trail twice in both types of gang-lines, pulling a quadbike on dry ground. Each dog remained in its team in the same position (side of gang line, and forward or back in the line) for both runs, using both types of lines in randomised order between the runs. Markers were placed on the dogs and on the main lines, and the runs were recorded by a video camera. The dogs’ angle of pull measured from the video recordings was compared between the two conditions. Thirteen positional measurements for each dog during each run were taken. The dogs were used to running in TRAD and were not acclimatised to STICK. Data was analysed using Wilcoxon and Spearmans rho tests. Data regarding individual dogs (n=13), teams (n=52), dogs’ placements in teams (n=4), and gang-line related pulling angles (n=104) was analysed. Overall, the position of the dogs was straighter when pulling in STICK, than when pulling in TRAD, with a median of 19° (inter quartile range (IQR) 24.75°) and 32° (IQR 25.75°), respectively (P<0.001). Between the two teams, there was no significant difference in pulling positions when running in STICK (P=0.543), but there was in TRAD (P<0.001). In individual assessment, six of the eight dogs ran in a straighter position (P=0.003 to 0.046) in STICK. Dogs running in the front of both teams pulled significantly straighter when in STICK (21°; IQR 23.75) than in TRAD (median 39°; IQR 18; P<0.001).

P096 Pregnancy outcomes in women attending a joint obstetric and rheumatology clinic in a tertiary centre over a 2-year period

Background/Aims The Lupus in Pregnancy Scanning (LIPS) clinic, a joint obstetrics and rheumatology clinic was established in 2010 at Saint Mary’s Hospital, Manchester, UK for women with systemic lupus erythematosus (SLE) and other complex rheumatological conditions. We aimed to describe pregnancy outcomes of women attending this clinic to establish a baseline for future changes aimed at improving the service. Methods Data were collected retrospectively from electronic records of patients who attended the LIPS clinic at least once between 1st January 2018 and 31st December 2019. Results Pregnancy outcomes were available in 105/125 (84%) women (Table). The median age [inter-quartile range] was 30.6 years [IQR 27.7 - 33.6] and 40 (38%) were of non-Caucasian background. Sixty-one (58%) had a connective tissue disease (CTD) of whom 36 (59%) had SLE. Other rheumatological diagnoses included inflammatory arthritis, primary anti-phospholipid syndrome (APS) and systemic vasculitis. Anti-Ro was found in 32 (31%) and anti-phospholipid antibodies in 25 (24%). During pregnancy, 65 (62%) received aspirin and 40 (38%) had low molecular weight heparin (LMWH). In the antenatal period, 43 (41%) took steroids, 52 (50%) had conventional disease modifying anti-rheumatic drugs and 8 (8%) received biologics. Active disease in the antenatal period was noted in 14 (13%) women. Regarding pregnancy outcomes (Table), still-births were low (0.95%). The rate of C-sections (45%) and assisted deliveries (19.6%) was comparable to previously published data from similar clinics. P096 Table 1:Pregnancy outcomes over a 2-year period in women attending the LIPS clinic at St. Mary's HospitalPregnancy Outcomen (%)Miscarriage3 (2.9)Deliveries• Live101 (96.2)• Still-birth1 (0.95)Median Gestation (weeks) [inter-quartile range (IQR)]38 [37 - 39]Sex of Neonate• Female57 (56)• Male45 (44)Mode of Delivery• Normal vaginal36 (35.3)• Assisted20 (19.6)• Elective Caesarean Section15 (14.7)• Emergency Caesarean Section31 (30.4)Median Neonatal Birth Weight (grams) [IQR]3137 [2724 - 3428]• Low Birth Weight &lt;2500g15 (15)Maternal Complications (Antenatal and Peri-Partum)• Infection22 (22)• Pre-Eclampsia1 (1)• Post-Partum Haemorrhage56 (55)Neonatal Intensive Care Admission7 (7)Neonatal Complications• Sepsis1 (1)• Congenital Heart Block2 (2)• Prematurity (&lt;36 weeks)39 (38) Conclusion In this cohort we report a high live birth rate and comparable rates of assisted delivery to similar cohorts. Infection and post-partum haemorrhage are maternal complications that are common, and reflect the complex clinical presentations and therapeutic regimes in these conditions. Overall this specialist clinic achieves favourable maternal and foetal outcomes in this high-risk population. Disclosure T. David: None. R. Hum: None. Y. Lau: None. S. Thornber: None. L. Simcox: None. I. Bruce: None. C. Tower: None. P. Ho: None.

Ice Roughness Estimation via Remotely Piloted Aircraft and Photogrammetry

Structure-from-Motion Photogrammetry conducted with images obtained via Remotely Piloted Aircraft (RPA) has revolutionized the field of land surface monitoring. RPA-Photogrammetry can quickly and easily capture a full 3D representation of a study area. The result of this process is a high-definition Digital Elevation Model (DEM) representing the land surface of a given study area. It is particularly useful in applications where land surface data collection would otherwise be expensive or dangerous. The monitoring of fluvial ice covers can be time-intensive, dangerous, and costly, if detailed data are required. Fluvial ice roughness is a sensitive parameter in hydraulic models and is incredibly difficult to measure directly using traditional field methods. This research hypothesized that the surface roughness of a newly-frozen fluvial ice cover is indicative of subsurface roughness. The hypothesis was tested through a comparison of ice roughness determined through the statistical analysis of RPA-photogrammetry DEMs to ice roughness values predicted by the Nezhikhovskiy equation. The Nezhikhovskiy equation is a widely used empirical method for estimating ice roughness based on observed ice thickness. Hydraulic and topographic data were collected over two years of field research on the Dauphin River in Manitoba, Canada. Various statistical metrics were used to represent the roughness of the DEMs. Strong trends were identified in the comparison of ice cover roughness values determined through RPA-photogrammetry and those calculated via the Nezhikhovskiy equation, as well as with ice thickness. The inter-quartile range of observed roughness heights was determined to be the most representative roughness metric. The maximum peak value performed better in some cases, but the fact that this metric would be heavily influenced by outliers led to it being rejected as a representative metric. Three distinct forms of surface ice roughness were noted: rough, smooth, and ridged. Statistical properties of the DEMs of fluvial ice covers were calculated. No DEMs were found to be normally distributed. k-means clustering analysis was used to group sampled data into two categories, which were interpreted as rough and smooth ice. The inter-quartile range of the smooth and rough categories were found to be 0.01–0.05 meters and 0.07–0.12 meters, respectively. RPA-photogrammetry was concluded to be a suitable method for the monitoring of fluvial ice covers. Other applications of RPA-photogrammetry for the characterization of fluvial ice covers are proposed.

Association between Primary Perioperative CEA Ratio, Tumor Site, and Overall Survival in Patients with Colorectal Cancer

There are differences in the incidence, clinical presentation, molecular pathogenesis, and outcome of colorectal cancer (CRC) based on tumor location. Emerging research suggests that the perioperative carcinoembryonic antigen (CEA) ratio (post-op/pre-op CEA) is a prognostic factor for CRC patients. We aimed to determine the association between CEA ratio, tumor location, and overall survival (OS) among patients with CRC. We analyzed 427 patients who underwent resection for CRC at the University of Kansas Medical Center. After excluding those without pre- or post-operative CEA data, 207 patients were classified as either high (≥0.5) or low (<0.5) ratio. Primary outcomes were as follows: (1) OS stratified by CEA ratio; (2) OS stratified by tumor location; (3) OS stratified by tumor location among those with CEA elevation > 5 ng/mL at the time of recurrence. The Kaplan–Meier method was used to estimate survival rates. The median age was 62 years (inter-quartile range 51–71), 55% were male, 41% were smokers, 71% had left-sided tumors, the median pre-operative CEA was 3.1 ng/mL (inter-quartile range (IQR) 1.5–9.7), and 57% had a CEA ratio ≥0.5. The OS rates were 65.1% and 86.3% in patients with high versus low CEA ratios, respectively (log-rank p-value = 0.045). The OS rates were 64.4% and 77.3% in patients with right-sided vs. left-sided tumors, respectively (log-rank p-value = 0.5). Among patients with CEA levels greater than 5 at the time of recurrence, the OS rates were 42.9% and 43.4% in patients with right-sided vs. left-sided tumors, respectively (log-rank p-value = 0.7). There was a significantly higher survival among patients with low CEA ratios than among those with high CEA ratios. There was no difference in OS between left- versus right-sided tumors. Among patients with CEA elevation > 5 ng/mL at the time of recurrence, there was no difference in OS between left versus right-sided tumors. These findings warrant validation in a larger cohort as our sample size was limited.

Biomarkers in patients with cryptogenic stroke/TIA and subclinical atrial fibrillation

Background A large proportion of patients with cryptogenic stroke or transitory ischemic attack (TIA) have underlying subclinical atrial fibrillation (SCAF) detected on follow up. It is not clear whether SCAF is the underlying primary entity in the pathogenesis of stroke in these patients, or merely a marker of atrial myopathy associated with left atrial remodeling, fibrosis and inflammation. Purpose As a hypothesis generating study, we investigated a panel of selected biomarkers involved in fibrosis, inflammation, and thrombosis: growth differentiation factor 15 (GDF-15), transforming growth factor b (TGFb), galectin-3, soluble suppressor of tumorgenicity2 (sST2), von Willebrand factor (vWF), Tissue metalloprotease1 (TIMP1), Matrix metalloprotease9 (MMP9), Emmprin, Interleukin6 (IL6), C-reactive protein (CRP), Tissue factor (TF), Plasminogen activator inhibitor (PAI1), and their relation to the occurrence of SCAF during follow-up in patients after cryptogenic stroke or TIA. We hypothized that biomarker levels were increased in patients with subclinical AF. Methods 236 patients, median age 71 years (range 21–94) of which 38% were women, with their first cryptogenic stroke or TIA were included 2–4 days after the index event and followed with an Implantable Cardiac Rhythm Monitor for &gt;1 year. Echocardiography and blood sampling were performed at inclusion. ELISA methods were used. Results SCAF occurred in 84 patients (36%). Only GDF-15 was significantly increased in AF- vs no-AF patients: 1010 pg/mL (inter quartile range: 814–1416) vs 860 pg/mL (inter quartile range: 622–1197) (p=0.018), and correlated with the number of premature atrial contractions (PAC)/24h (by Holter ECG during index hospitalization) (rs=0.314, p&lt;0.001) and AF-burden during follow-up (rs=0.149, p=0.022). Furthermore, there was a significant trend across quartiles of GDF-15 for having AF, and patients in the three highest quartiles (Q2–4) compared with Q1 had an odd ratio of having AF of 2.16 (95% CI 1.10–4.25), adjusted for sex and body mass index. The significance, however, was lost when adjusting for age, which correlated significantly to GDF-15 (rs=0.283; p&lt;0.001). ROC curve analyses showed an AUC of 0.593 (0.52–0.68) for GDF-15 compared to 0.617 (0.54–0.69) for age. GDF-15 was also associated with co-morbidities such as hypertension (p&lt;0.001), diabetes (p&lt;0.001), and vascular disease (p&lt;0.001). Conclusion In patients with a cryptogenic stroke or TIA experiencing SCAF during follow up, only levels of GDF-15 were elevated and correlated with PAC/24h and AF-burden. However, GDF-15 was highly related to age and co-morbidities and did not add significantly to the prediction of AF in a multivariate analysis. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Stiftelsen Dam, Norwegian Atrial Fibrillation Research Network

A Strength and Weakness of Regression Analysis and Quartile and IQR Deviation by using Test- Driven Development

Test-Driven Development (TDD) derives an evolutionary approach which needs unit test cases to be made before implementation of the code. The goal of this paper is to examine product code quality and programmer productivity using test-driven development approach. This paper establishes regression analysis and quartile & inter-quartile range deviation to evaluate the process effect on external code quality and developer productivity. The results of this paper are that if developer productivity is the actual effect, external code quality will be fewer decreased and external code quality is the actual effect if developer productivity will be fewer reduced. Test-Driven Development can produce the clear of code, simple and bug-release. Defect numbers decreased when automated unit tests are written iteration related to test-driven development. If necessary, the code refactoring is acted TDD. This proposed system evaluates regression analysis and quartile & inter-quartile range deviation based on a fixed time-frame.

Patterns of Racing and Career Duration of Racing Greyhounds in New Zealand

The welfare and wastage of racing greyhounds is a topic of public concern. Little is published about the racing patterns of these dogs in New Zealand. The aim of this study is to describe the pattern of greyhound racing in New Zealand. Data on all race starts between 1 August 2011 and 25 March 2018 were supplied by Greyhound Racing New Zealand. A cohort was created containing dogs that had a racing career between 1 August 2013 and 31 July 2017. Data were collated within a customized Microsoft Access database from electronic records of all racing starts for every dog within the 2013–2016 racing seasons. For this cohort of racing dogs, there were 97,973 race starts across 22,277 races involving 2393 individual greyhounds. The median number of days between racing starts was 7 days (inter-quartile range (IQR): 4–10 days). The median career length was 424 days (IQR: 206–647 days) and the median number of racing starts throughout a racing career was 35 (IQR: 16–59 starts). Dogs of similar ability finished their career at a similar age.