Machine learning methods for the modelling and optimisation of biogas production from anaerobic digestion: a review.

Biogas plant operators often face huge challenges in the monitoring, controlling and optimisation of the anaerobic digestion (AD) process, as it is very sensitive to surrounding changes, which often leads to process failure and adversely affects biogas production. Conventional implemented methods and mechanistic models are impractical and find it difficult to model the nonlinear and intricate interactions of the AD process. Thus, the development of machine learning (ML) algorithms has attracted considerable interest in the areas of process optimization, real-time monitoring, perturbation detection and parameter prediction. This paper provides a comprehensive and up-to-date overview of different machine learning algorithms, including artificial neural network (ANN), fuzzy logic (FL), adaptive network-based fuzzy inference system (ANFIS), support vector machine (SVM), genetic algorithm (GA) and particle swarm optimization (PSO) in terms of working mechanism, structure, advantages and disadvantages, as well as their prediction performances in modelling the biogas production. A few recent case studies of their applications and limitations are also critically reviewed and compared, providing useful information and recommendation in the selection and application of different ML algorithms. This review shows that the prediction efficiency of different ML algorithms is greatly impacted by variations in the reactor configurations, operating conditions, influent characteristics, selection of input parameters and network architectures. It is recommended to incorporate mixed liquor volatile suspended solids (MLVSS) concentration of the anaerobic digester (ranging from 16,500 to 46,700 mg/L) as one of the input parameters to improve the prediction efficiency of ML modelling. This review also shows that the combination of different ML algorithms (i.e. hybrid GA-ANN model) could yield better accuracy with higher R2 (0.9986) than conventional algorithms and could improve the optimization model of AD. Besides, future works could be focused on the incorporation of an integrated digital twin system coupled with ML techniques into the existing Supervisory Control and Data Acquisition (SCADA) system of any biogas plant to detect any operational abnormalities and prevent digester upsets.

Non-invasive mid-term electrocardiogram patch monitoring is effective in detecting atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is a cause of serious morbidity such as stroke. Early detection and treatment of AF is important. Current guidelines recommend screening via opportunistic pulse taking or 12­lead electrocardiogram. Mid-term ECG patch monitors increases the sensitivity of AF detection. METHODS: The Singapore Atrial Fibrillation Study is a prospective multi-centre study aiming to study the incidence of AF in patients with no prior AF and a CHA2DS2-VASc score of at least 1, with the use of a mid-term continuous ECG monitoring device (Spyder ECG). Consecutive patients from both inpatient and outpatient settings were recruited from 3 major hospitals from May 2016 to December 2019. RESULTS: Three hundred and fifty-five patients were monitored. 6 patients (1.7%) were diagnosed with AF. There were no significant differences in total duration of monitoring between the AF and non-AF group (6.39 ± 3.19 vs 5.42 ± 2.46 days, p = 0.340). Patients with newly detected AF were more likely to have palpitations (50.0% vs 11.8%, p = 0.027). Half of the patients (n = 3, 50.0%) were diagnosed on the first day of monitoring and the rest were diagnosed after 24 h. On univariate analysis, only hyperlipidemia was associated with reduced odds of being diagnosed with AF (OR HR 0.08 CI 0.01-0.74, p = 0.025). In a group of 128 patients who underwent coronary artery bypass grafting and had post-operative ECG monitoring, 9 patients (7.0%) were diagnosed with post-operative AF. CONCLUSIONS: The use of non-invasive mid-term patch-based ECG monitoring is an effective modality for AF screening.

Single-photon avalanche diode fabricated in standard 55†nm bipolar-CMOS-DMOS technology with sub-20†V breakdown voltage.

This paper presents a single-photon avalanche diode (SPAD) in 55 nm bipolar-CMOS-DMOS (BCD) technology. In order to realize a SPAD having sub-20 V breakdown voltage for mobile applications while preventing high tunneling noise, a high-voltage N-well available in BCD is utilized to implement the avalanche multiplication region. The resulting SPAD has a breakdown voltage of 18.4 V while achieving an excellent dark count rate of 4.4 cps/µm2 at the excess bias voltage of 7 V in spite of the advanced technology node. At the same time, the device achieves a high peak photon detection probability (PDP) of 70.1% at 450 nm thanks to the high and uniform E-field. Its PDP values at 850 and 940 nm, wavelengths of interest for 3D ranging applications reach 7.2 and 3.1%, respectively, with the use of deep N-well. The timing jitter of the SPAD, full width at half maximum (FWHM), is 91 ps at 850 nm. It is expected that the presented SPAD enables cost-effective time-of-flight and LiDAR sensors with the advanced standard technology for many mobile applications.

Selective Anomeric Acetylation of Unprotected Sugars with Acetic Anhydride in Water.

Unprotected sugars are selectively acetylated simply by stirring in aqueous solution in the presence of acetic anhydride and a weak base such as sodium carbonate. The reaction is selective for acetylation of the anomeric hydroxyl group of mannose, 2-acetamido, and 2-deoxy sugars and can be performed on a large scale. Competitive intramolecular migration of the 1-O-acetate to the 2-hydroxyl group when these two substituents are cis causes over-reaction and the formation of product mixtures.

Outcomes of Investigating T Wave Inversion With Echocardiography in an Unselected Young Male Preparticipation Cohort.

BACKGROUND Electrocardiography (ECG) may be performed as part of preparticipation sports screening. Recommendations on screening of athletes to identify individuals with previously unrecognized cardiac disease are robust; however, data guiding the preparticipation screening of unselected populations are scarce. T wave inversion (TWI) on ECG may suggest an undiagnosed cardiomyopathy. This study aims to describe the prevalence of abnormal TWI in an unselected young male cohort and the outcomes of an echocardiography-guided approach to investigating these individuals for structural heart diseases, focusing on the yield for cardiomyopathies. METHODS AND RESULTS Consecutive young male individuals undergoing a national preparticipation cardiac screening program for 39 months were studied. All underwent resting supine 12-lead ECG. Those manifesting abnormal TWI, defined as negatively deflected T waves of at least 0.1 mV amplitude in any 2 contiguous leads, underwent echocardiography. A total of 69 714 male individuals with a mean age of 17.9±1.1 years were studied. Of the individuals, 562 (0.8%) displayed abnormal TWI. This was most frequently observed in the anterior territory and least so in the lateral territory. A total of 12 individuals (2.1%) were diagnosed with a cardiomyopathy. Cardiomyopathy diagnoses were significantly associated with deeper maximum TWI depth and the presence of abnormal TWI in the lateral territory, but not with abnormal TWI in the anterior and inferior territories. No individual presenting with TWI restricted to solely leads V1 to V2, 2 inferior leads or both was diagnosed with a cardiomyopathy. CONCLUSIONS Cardiomyopathy diagnoses were more strongly associated with certain patterns of abnormal TWI. Our findings may support decisions to prioritize echocardiography in these individuals.

A sub-wavelength Si LED integrated in a CMOS platform.

A nanoscale on-chip light source with high intensity is desired for various applications in integrated photonics systems. However, it is challenging to realize such an emitter using materials and fabrication processes compatible with the standard integrated circuit technology. In this letter, we report an electrically driven Si light-emitting diode with sub-wavelength emission area fabricated in an open-foundry microelectronics complementary metal-oxide-semiconductor platform. The light-emitting diode emission spectrum is centered around 1100 nm and the emission area is smaller than 0.14 µm2 (~[Formula: see text] nm). This light-emitting diode has high spatial intensity of >50 mW/cm2 which is comparable with state-of-the-art Si-based emitters with much larger emission areas. Due to sub-wavelength confinement, the emission exhibits a high degree of spatial coherence, which is demonstrated by incorporating the light-emitting diode into a compact lensless in-line holographic microscope. This centimeter-scale, all-silicon microscope utilizes a single emitter to simultaneously illuminate ~9.5 million pixels of a complementary metal-oxide-semiconductor imager.

Snakebite drug discovery: high-throughput screening to identify novel snake venom metalloproteinase toxin inhibitors.

Snakebite envenoming results in ∼100,000 deaths per year, with close to four times as many victims left with life-long sequelae. Current antivenom therapies have several limitations including high cost, variable cross-snake species efficacy and a requirement for intravenous administration in a clinical setting. Next-generation snakebite therapies are being widely investigated with the aim to improve cost, efficacy, and safety. In recent years several small molecule drugs have shown considerable promise for snakebite indication, with oral bioavailability particularly promising for community delivery rapidly after a snakebite. However, only two such drugs have entered clinical development for snakebite. To offset the risk of attrition during clinical trials and to better explore the chemical space for small molecule venom toxin inhibitors, here we describe the first high throughput drug screen against snake venom metalloproteinases (SVMPs)-a pathogenic toxin family responsible for causing haemorrhage and coagulopathy. Following validation of a 384-well fluorescent enzymatic assay, we screened a repurposed drug library of 3,547 compounds against five geographically distinct and toxin variable snake venoms. Our drug screen resulted in the identification of 14 compounds with pan-species inhibitory activity. Following secondary potency testing, four SVMP inhibitors were identified with nanomolar EC50s comparable to the previously identified matrix metalloproteinase inhibitor marimastat and superior to the metal chelator dimercaprol, doubling the current global portfolio of SVMP inhibitors. Following analysis of their chemical structure and ADME properties, two hit-to-lead compounds were identified. These clear starting points for the initiation of medicinal chemistry campaigns provide the basis for the first ever designer snakebite specific small molecules.

A racing heart post-Pfizer/BioNTech BNT162b2.

Palpitations is one of the most common side effects experienced post-messenger-RNA COVID-19 vaccines. However, some patients experience significant symptoms and further workup needs to be considered. We present an interesting case of inappropriate sinus tachycardia in a fit gentleman who presented with worsening palpitations and elevated heart rate post-first and -second dose of the Pfizer/BioNTech vaccine.

Development of a bioorthogonal fluorescence-based assay for assessing drug uptake and delivery in bacteria.

Bioorthogonal chemistry can facilitate the development of fluorescent probes that can be used to sensitively and specifically detect the presence of biological targets. In this study, such an assay was developed to evaluate the uptake and delivery of antimicrobials into Escherichia coli, building on and extending previous work which utilised more resource intensive LCMS detection. The bacteria were genetically engineered to express streptavidin in the periplasmic or cytoplasmic compartments, which was used to localise a bioorthogonal probe (BCN-biotin). Azido-compounds which are delivered to these compartments react with the localised BCN-biotin-streptavidin in a concentration-dependent manner via a strain-promoted alkyne-azide cycloaddition. The amount of azido-compound taken up by bacteria was determined by quantifying unreacted BCN-biotin-streptavidin via an inverse electron demand Diels-Alder reaction between remaining BCN-biotin and a tetrazine-containing fluorescent dye. Following optimisation and validation, the assay was used to assess uptake of liposome-formulated azide-functionalised luciferin and cefoxitin. The results demonstrated that formulation into cationic liposomes improved the uptake of azide-functionalised compounds into the periplasm of E. coli, providing insight on the uptake mechanism of liposomes in the bacteria. This newly developed bioorthogonal fluorescence plate-reader based assay provides a bioactivity-independent, medium-to-high throughput tool for screening compound uptake/delivery.

Initial experience of left bundle branch pacing using the Abbott Agilis HisPro Catheter with stylet-driven leads.

AIMS: Conduction system pacing has gained steady interest over recent years. While the majority of tools and delivery techniques were developed for His bundle pacing (HBP), the feasibility and reproducibility of using these similar tools for left bundle branch pacing (LBBP) has yet to be determined. We describe our technique for performing LBBP using the Abbott Agilis HisPro™ Steerable Catheter. METHODS AND RESULTS: A series of 22 patients with a mean age of 71.7 years (16 males, 72.7%), underwent LBBP procedure with this catheter between May and October 2021. Nineteen patients (86%) had successful LBBP lead implantation. There were no major complications or mortality. CONCLUSION: The Agilis HisPro™ catheter along with the stylet driven Tendril STS Model 2088TC lead is a safe and feasible delivery system for LBBP.

Outcomes of supraventricular tachycardia ablation: Results from the Singapore ablation and cardiac devices registry.

BACKGROUND: The Singapore Cardiac Databank was designed to monitor the performance and outcomes of catheter ablation. We investigated the outcomes of paroxysmal supraventricular tachycardia (PSVT)-ablation in a prospective, nationwide, cohort study. METHODS: Atrioventricular nodal re-entrant tachycardia (AVNRT), atrioventricular re-entry tachycardia (AVRT), or atrial tachycardia (AT)-ablations in Singapore from 2010 to 2018 were studied. Outcomes include acute success, periprocedural-complications, postoperative pacing requirement, arrhythmic recurrence and 1-year all-cause mortality. RESULTS: Among 2260 patients (mean age 45 ± 18 years, 50% female, 57% AVNRT, 37% AVRT, 6% AT), overall acute success rates of PSVT-ablation was 98.4% and increased in order of AT, AVRT, and AVNRT (p < .001). Periprocedural cardiac tamponade occurred in two AVRT patients. A total of 15 pacemakers (6 within first 30-days, 9 after 30-days) were implanted (seven AV block, eight sinus node dysfunction [SND]), with the highest incidence of pacemaker implantation after AT-ablation (5% vs. 0.6% AVNRT vs. 0.1% AVRT, p < .001). Repeat ablations (0.9% AVNRT, 7% AVRT, 4% AT, p < .001) were performed in 78 (3.5%) patients and 13 (0.6%) patients died within a year of ablation. Among outcomes considered adjusting for age, sex, PSVT-type and procedure-time, AT was independently associated with 6-fold increased odds of total (adjusted odds ratio [AOR] 6.32, 95% confidence interval [CI] 1.95-20.53) and late (AOR 6.38, 95% CI 1.39-29.29) pacemaker implantation, while AVRT was associated with higher arrhythmic recurrence with repeat ablations (AOR 4.72, 95% CI 2.36-9.44) compared to AVNRT. CONCLUSIONS: Contemporary PSVT ablation is safe with high acute success rates. Long-term outcomes differed by nature of the PSVT.

Direct Oral Anticoagulants in Asian Patients with Atrial Fibrillation: Consensus Recommendations by the Asian Pacific Society of Cardiology on Strategies for Thrombotic and Bleeding Risk Management.

The disease burden of AF is greater in Asia-Pacific than other areas of the world. Direct oral anticoagulants (DOACs) have emerged as effective alternatives to vitamin K antagonists (VKA) for preventing thromboembolic events in patients with AF. The Asian Pacific Society of Cardiology developed this consensus statement to guide physicians in the management of AF in Asian populations. Statements were developed by an expert consensus panel who reviewed the available data from patients in Asia-Pacific. Consensus statements were developed then put to an online vote. The resulting 17 statements provide guidance on the assessment of stroke risk of AF patients in the region, the appropriate use of DOACs in these patients, as well as the concomitant use of DOACs and antiplatelets, and the transition to DOACs from VKAs and vice versa. The periprocedural management of patients on DOAC therapy and the management of patients with bleeding while on DOACs are also discussed.

Development of Covalent, Clickable Probes for Adenosine A1 and A3 Receptors.

Adenosine receptors are attractive therapeutic targets for multiple conditions, including ischemia-reperfusion injury and neuropathic pain. Adenosine receptor drug discovery efforts would be facilitated by the development of appropriate tools to assist in target validation and direct receptor visualization in different native environments. We report the development of the first bifunctional (chemoreactive and clickable) ligands for the adenosine A1 receptor (A1R) and adenosine A3 receptor (A3R) based on an orthosteric antagonist xanthine-based scaffold and on an existing structure-activity relationship. Bifunctional ligands were functional antagonists with nanomolar affinity and irreversible binding at the A1R and A3R. In-depth pharmacological profiling of these bifunctional ligands showed moderate selectivity over A2A and A2B adenosine receptors. Once bound to the receptor, ligands were successfully "clicked" with a cyanine-5 fluorophore containing the complementary "click" partner, enabling receptor detection. These bifunctional ligands are expected to aid in the understanding of A1R and A3R localization and trafficking in native cells and living systems.

Machine learning versus classical electrocardiographic criteria for echocardiographic left ventricular hypertrophy in a pre-participation cohort.

BACKGROUND: Classical electrocardiographic (ECG) criteria for left ventricular hypertrophy (LVH) are well studied in older populations and patients with hypertension. Their utility in young pre-participation cohorts is unclear. AIMS: We aimed to develop machine learning models for detection of echocardiogram-diagnosed LVH from ECG, and compare these models with classical criteria. METHODS: Between November 2009 and December 2014, pre-participation screening ECG and subsequent echocardiographic data was collected from 17 310 males aged 16 to 23, who reported for medical screening prior to military conscription. A final diagnosis of LVH was made during echocardiography, defined by a left ventricular mass index >115 g/m2. The continuous and threshold forms of classical ECG criteria (Sokolow-Lyon, Romhilt-Estes, Modified Cornell, Cornell Product, and Cornell) were compared against machine learning models (Logistic Regression, GLMNet, Random Forests, Gradient Boosting Machines) using receiver-operating characteristics curve analysis. We also compared the important variables identified by machine learning models with the input variables of classical criteria. RESULTS: Prevalence of echocardiographic LVH in this population was 0.82% (143/17310). Classical ECG criteria had poor performance in predicting LVH. Machine learning methods achieved superior performance: Logistic Regression (area under the curve [AUC], 0.811; 95% confidence interval [CI], 0.738-0.884), GLMNet (AUC, 0.873; 95% CI, 0.817-0.929), Random Forest (AUC, 0.824; 95% CI, 0.749-0.898), Gradient Boosting Machines (AUC, 0.800; 95% CI, 0.738-0.862). CONCLUSIONS: Machine learning methods are superior to classical ECG criteria in diagnosing echocardiographic LVH in the context of pre-participation screening.

Singapore Advanced Cardiac Life Support Guidelines 2021.

Advanced cardiac life support (ACLS) emphasises the use of advanced airway management and ventilation, circulatory support and the appropriate use of drugs in resuscitation, as well as the identification of reversible causes of cardiac arrest. Extracorporeal cardiopulmonary resuscitation and organ donation, as well as special circumstances including drowning, pulmonary embolism and pregnancy are addressed. Resuscitation does not end with ACLS but must continue in post-resuscitation care. ACLS also covers the recognition and management of unstable pre-arrest tachy- and bradydysrhythmias that may deteriorate further.

Reporting of alcohol as a contributor to death in Australian national suicide statistics and its relationship to post-mortem alcohol concentrations.

AIM: To describe the assignment of International Classification of Disease (ICD)-10 alcohol codes as underlying or contributory causes of death by the Australian Bureau of Statistics during mortality coding for suicides according to the blood alcohol concentration (BAC) detected at autopsy. DESIGN: Population-based case-series descriptive analysis. SETTING AND PARTICIPANTS: Data for all alcohol-related (Alc+) suicide deaths (aged 15+) in Australia from 2010-2015 (n = 3132) from the National Coronial Information System. MEASUREMENTS: Alc+ suicides were categorised as those with a post-mortem BAC ≥0.05 g/100 mL. The outcome variable was whether the case was assigned an ICD-10 alcohol code (F10.0-F10.9, R78.0, T51, X45 and/or X65). We estimated OR for the assignment of codes in Alc+ suicides using BAC as the key predictor. We also examined several covariates that have been implicated in the risk of Alc+ suicides. FINDINGS: An ICD-10 alcohol code was assigned during the mortality coding process in 47.6% (n = 1491) of Alc+ suicides. Higher BAC was associated with higher odds of having a code assigned; cases with a BAC over 0.20 g/100 mL over were twice as likely to have an alcohol code assigned (adjusted OR [AOR] = 2.06, 95% CI = 1.59, 2.67) compared with cases with a BAC of 0.050-0.075 g/100 mL. Compared with New South Wales, higher likelihood of code assignment was found in Northern Territory (AOR = 3.85, 95% CI = 2.32, 6.63) and Western Australia (AOR = 2.89, 95% CI = 2.27, 3.68). Compared with 15-24 year olds, 25-44 (AOR = 0.79, 95% CI = 0.63, 0.99) and 65-84 year olds (AOR = 0.63, 95% CI = 0.43, 0.93) were less likely to have a code assigned. CONCLUSIONS: An ICD-10 alcohol code was not assigned as an underlying or contributory cause of death in over half of suicides in Australia (2010-2015) with a BAC ≥0.05 g/100 mL. The higher the BAC detected at autopsy, the more likely cases were to be assigned an alcohol code during the mortality coding process.

Parameterization of metabolite and macromolecule contributions in interrelated MR spectra of human brain using multidimensional modeling.

Macromolecular signals are crucial constituents of short echo-time 1 H MR spectra with potential clinical implications in themselves as well as essential ramifications for the quantification of the usually targeted metabolites. Their parameterization, needed for general fitting models, is difficult because of their unknown composition. Here, a macromolecular signal parameterization together with metabolite signal quantification including relaxation properties is investigated by multidimensional modeling of interrelated 2DJ inversion-recovery (2DJ-IR) datasets. Simultaneous and iterative procedures for defining the macromolecular background (MMBG) as mono-exponentially or generally decaying signals over TE are evaluated. Varying prior knowledge and restrictions in the metabolite evaluation are tested to examine their impact on results and fitting stability for two sets of three-dimensional spectra acquired with metabolite-cycled PRESS from cerebral gray and white matter locations. One dataset was used for model optimization, and also examining the influence of prior knowledge on estimated parameters. The most promising model was applied to a second dataset. It turned out that the mono-exponential decay model appears to be inadequate to represent TE-dependent signal features of the MMBG. TE-adapted MMBG spectra were therefore determined. For a reliable overall quantification of implicated metabolite concentrations and relaxation times, a general fitting model had to be constrained in terms of the number of fitting variables and the allowed parameter space. With such a model in place, fitting precision for metabolite contents and relaxation times was excellent, while fitting accuracy is difficult to judge and bias was likely influenced by the type of fitting constraints enforced. In summary, the parameterization of metabolite and macromolecule contributions in interrelated MR spectra has been examined by using multidimensional modeling on complex 2DJ-IR datasets. A tightly restricted model allows fitting of individual subject data with high fitting precision documented in small Cramér-Rao lower bounds, good repeatability values and a relatively small spread of estimated concentration and relaxation values for a healthy subject cohort.

A Population-wide study of electrocardiographic (ECG) norms and the effect of demographic and anthropometric factors on selected ECG characteristics in young, Southeast Asian males-results from the Singapore Armed Forces ECG (SAFE) study.

BACKGROUND: Routine use of pre-participation electrocardiograms (ECGs) has been used by the Singapore Armed Forces, targeting early detection of significant cardiac diseases. We aim to describe the impact of demographic and anthropometric factors on ECG variables and establish a set of electrocardiographic reference ranges specific to a young male multiethnic Southeast Asian cohort. METHODS AND RESULTS: Between November 1, 2009, and December 31, 2014, 144,346 young male conscripts underwent pre-participation screening that included a 12-lead ECG, demographic and anthropometric measurements. The Chinese population had the longest PR interval (146.7 ± 19.7 vs. 145.21 ± 19.2 in Malays vs. 141.2 ± 18.8 ms in Indians), QRS duration (94.5 ± 9.8 vs. 92.6 ± 9.7 in Malays vs. 92.5 ± 9.4 ms in Indians) and QTcB interval (408.3 ± 21.3 vs. 403.5 ± 21.6 in Malays vs. 401.2 ± 21.4 ms in Indians) (all p < 0.001). Body mass index (BMI) >25 kg/m2 and body fat >25% were independently associated with lower prevalence of increased QRS voltage on ECG. Systolic blood pressure of >140 mmHg or diastolic blood pressure of >90 mmHg independently increased the prevalence of increased QRS voltage on ECG. CONCLUSIONS: Electrocardiographic parameters vary across different ethnicities and in comparison with international norms. In our population, diagnosis of increased QRS voltage by ECG is less prevalent with obesity and increased body fat. Further analysis of gold standard measurements for the diagnosis of LVH in our population is ongoing, to improve the accuracy of the ECG screening process.