Delayed application of GDNF can decrease the NOS expression and rescue injured motor neurons in adult rat with C7 spinal root avulsion

INTRODUCTION: Our previous studies have shown that spinal motoneurons express neuronal NOS and then die following root avulsion injury. Expression of nNOS and death of spinal motoneurons due to root avulsion can be prevented if ...published_or_final_versio

Association of specific language impairment candidate genes CMIP and ATP2C2 with developmental dyslexia in Chinese population

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Association study of stuttering candidate genes GNPTAB, GNPTG and NAGPA with dyslexia in Chinese population

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Territory-Wide Chinese Cohort of Long QT Syndrome: Random Survival Forest and Cox Analyses

Introduction: Congenital long QT syndrome (LQTS) is a cardiac ion channelopathy that predisposes affected individuals to spontaneous ventricular tachycardia/fibrillation (VT/VF) and sudden cardiac death (SCD). The main aims of the study were to: (1) provide a description of the local epidemiology of LQTS, (2) identify significant risk factors of ventricular arrhythmias in this cohort, and (3) compare the performance of traditional Cox regression with that of random survival forests. / Methods: This was a territory-wide retrospective cohort study of patients diagnosed with congenital LQTS between 1997 and 2019. The primary outcome was spontaneous VT/VF. / Results: This study included 121 patients [median age of initial presentation: 20 (interquartile range: 8–44) years, 62% female] with a median follow-up of 88 (51–143) months. Genetic analysis identified novel mutations in KCNQ1, KCNH2, SCN5A, ANK2, CACNA1C, CAV3, and AKAP9. During follow-up, 23 patients developed VT/VF. Univariate Cox regression analysis revealed that age [hazard ratio (HR): 1.02 (1.01–1.04), P = 0.007; optimum cut-off: 19 years], presentation with syncope [HR: 3.86 (1.43–10.42), P = 0.008] or VT/VF [HR: 3.68 (1.62–8.37), P = 0.002] and the presence of PVCs [HR: 2.89 (1.22–6.83), P = 0.015] were significant predictors of spontaneous VT/VF. Only initial presentation with syncope remained significant after multivariate adjustment [HR: 3.58 (1.32–9.71), P = 0.011]. Random survival forest (RSF) model provided significant improvement in prediction performance over Cox regression (precision: 0.80 vs. 0.69; recall: 0.79 vs. 0.68; AUC: 0.77 vs. 0.68; c-statistic: 0.79 vs. 0.67). Decision rules were generated by RSF model to predict VT/VF post-diagnosis. / Conclusions: Effective risk stratification in congenital LQTS can be achieved by clinical history, electrocardiographic indices, and different investigation results, irrespective of underlying genetic defects. A machine learning approach using RSF can improve risk prediction over traditional Cox regression models

Arrhythmic Outcomes in Catecholaminergic Polymorphic Ventricular Tachycardia

Introduction Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare cardiac ion channelopathy. The aim of this study is to examine the genetic basis and identify pre-dictive factors for arrhythmic outcomes in CPVT patients from Hong Kong. Methods This was a territory-wide retrospective cohort study of consecutive patients diagnosed with CPVT at public hospitals or clinics in Hong Kong. The primary outcome was spontaneous ventricular tachycardia/ventricular fibrillation (VT/VF). Results A total of 16 (mean presentation age=11±4 years old) patients were included. All patients presented at or before 19 years of age. Fifteen patients (93.8%) were initially symptomatic. Ten patients had both premature ventricular complexes (PVCs) and VT/VF, whereas one patient had PVCs without VT/VF. Genetic tests were performed in 14 patients (87.5%). Eight (57.1%) tested positive for the RyR2 gene. Seven variants have been described else-where (c.14848G>A, c.12475C>A, c.7420A>G, c.11836G>A, c.14159T>C, c.10046C>T and c.7202G>A). c.14861C>G is a novel RyR2 variant that has not been reported outside this cohort. All patients were treated with beta-blockers, three patients received amiodarone and two received verapamil. Sympathectomy (n=8), ablation (n=1) and implantable-cardioverter defibrillator implantation (n=3) were performed. Over a median follow-up of 127 (IQR: 97-143) months, six patients suffered from incident VT/VF. No significant predictors were identified on Cox regression. Nevertheless, a random survival forest model identified initial VT/VF/sudden cardiac death, palpitations, QTc, initially symptomatic and heart rate as important variables for estimating the probability of developing incident VT/VF. Conclusion All CPVT patients who are from Hong Kong presented at or before 19 years of age. Clinical and electrocardiographic findings can be used to predict arrhythmic outcomes. A nonparametric machine learning survival analysis achieved high accuracy for predicting the probability of incident VT/VF

Relationship between angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and COVID-19 incidence or severe disease

BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) may be associated with higher susceptibility of COVID-19 infection and adverse outcomes. We compared ACEI/ARB use and COVID-19 positivity in a case-control design, and severity in COVID-19 positive patients. METHODS: Consecutive patients who attended Hong Kong's public hospitals or outpatient clinics between 1 January and 28 July 2020 for COVID-19 real time-PCR (RT-PCR) tests were included. Baseline demographics, past comorbidities, laboratory tests and use of different medications were compared between COVID-19 positive and negative patients. Severe endpoints for COVID-19 positive patients were 28-day mortality, need for intensive care admission or intubation. RESULTS: This study included 213 788 patients (COVID-19 positive: n = 2774 patients; negative: n = 211 014). In total, 162 COVID-19 positive patients (5.83%) met the severity outcome. The use of ACEI/ARB was significantly higher amongst cases than controls (n = 156/2774, 5.62 vs. n = 6708/211014, 3.17%; P 1, P  0.05). CONCLUSION: There was a significant relationship between ACEI/ARB use and COVID-19 positivity and severe disease after adjusting for significant confounders

Probabilistic Models to Describe the Dynamics of Migrating Microbial Communities

In all but the most sterile environments bacteria will reside in fluid being transported through conduits and some of these will attach and grow as biofilms on the conduit walls. The concentration and diversity of bacteria in the fluid at the point of delivery will be a mix of those when it entered the conduit and those that have become entrained into the flow due to seeding from biofilms. Examples include fluids through conduits such as drinking water pipe networks, endotracheal tubes, catheters and ventilation systems. Here we present two probabilistic models to describe changes in the composition of bulk fluid microbial communities as they are transported through a conduit whilst exposed to biofilm communities. The first (discrete) model simulates absolute numbers of individual cells, whereas the other (continuous) model simulates the relative abundance of taxa in the bulk fluid. The discrete model is founded on a birth-death process whereby the community changes one individual at a time and the numbers of cells in the system can vary. The continuous model is a stochastic differential equation derived from the discrete model and can also accommodate changes in the carrying capacity of the bulk fluid. These models provide a novel Lagrangian framework to investigate and predict the dynamics of migrating microbial communities. In this paper we compare the two models, discuss their merits, possible applications and present simulation results in the context of drinking water distribution systems. Our results provide novel insight into the effects of stochastic dynamics on the composition of non-stationary microbial communities that are exposed to biofilms and provides a new avenue for modelling microbial dynamics in systems where fluids are being transported

Incident heart failure and myocardial infarction in sodium-glucose cotransporter 2 versus dipeptidyl peptidase-4 inhibitor users

Objectives To compare the rates of major cardiovascular adverse events in sodium-glucose cotransporter-2 inhibitors (SGLT2I) and dipeptidyl-peptidase-4 inhibitors (DPP4I) users in a Chinese population. Background SGLT2I and DPP4I are increasingly prescribed for type 2 diabetes mellitus patients. However, few population-based studies are comparing their effects on incident heart failure or myocardial infarction. Methods This was a population-based retrospective cohort study using the electronic health record database in Hong Kong, including type 2 diabetes mellitus patients receiving either SGLT2I or DPP4I between January 1st, 2015, to December 31st, 2020. Propensity-score matching was performed in a 1:1 ratio based on demographics, past comorbidities, non-SGLT2I/DPP4I medications with nearest-neighbor matching (caliper=0.1). Univariable and multivariable Cox models were used to identify significant predictors for new onset heart failure, new onset myocardial infarction, cardiovascular mortality, and all-cause mortality. Sensitivity analyses with competing risk models and multiple propensity score matching approaches were conducted. Subgroup age and gender analyses were presented. Results A total of 41994 patients (58.89% males, median admission age at 58 years old, interquartile rage [IQR]: 51.2-65.3) were included in the study cohorts with a median follow-up duration of 5.6 years (IQR: 5.32-5.82). After adjusting for significant demographics, past comorbidities, medication prescriptions and biochemical results, SGLT2I users have a significantly lower risk for myocardial infarction (hazard ratio [HR]: 0.34, 95% confidence interval [CI]: [0.28, 0.41], P < 0.0001), cardiovascular mortality (HR: 0.53, 95% CI: [0.38, 0.74], P = 0.0002) and all-cause mortality (HR: 0.21, 95% CI: [0.18, 0.25], P= 0.0001) under multivariable Cox regression. However, the risk for heart failure is comparable (HR: 0.87, 95% CI: [0.73, 1.04], P= 0.1343). Conclusions SGLT2 inhibitors are protective against adverse cardiovascular events compared to DPP4I. The prescription of SGLT2I is preferred especially for males and patients aged 65 or older to prevent cardiovascular risks

Sybil tolerance and probabilistic databases to compute web services trust

© Springer International Publishing Switzerland 2015. This paper discusses how Sybil attacks can undermine trust management systems and how to respond to these attacks using advanced techniques such as credibility and probabilistic databases. In such attacks end-users have purposely different identities and hence, can provide inconsistent ratings over the same Web Services. Many existing approaches rely on arbitrary choices to filter out Sybil users and reduce their attack capabilities. However this turns out inefficient. Our approach relies on non-Sybil credible users who provide consistent ratings over Web services and hence, can be trusted. To establish these ratings and debunk Sybil users techniques such as fuzzy-clustering, graph search, and probabilistic databases are adopted. A series of experiments are carried out to demonstrate robustness of our trust approach in presence of Sybil attacks

Pacific warm pool excitation, earth rotation and El Niño southern oscillations

2002-2003 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe