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In this paper, we have implemented a large-scale agent-based model to study the outbreak of coronavirus infectious diseases (COVID-19) in Singapore, taking into account complex human interaction pattern. In particular, the concept of multiplex network is utilized to differentiate between social interactions that happen in households and workplaces. In addition, weak interactions among crowds, transient interactions within social gatherings, and dense human contact between foreign workers in dormitories are also taken into consideration. Such a categorization in terms of a multiplex of social network connections together with the Susceptible-Exposed-Infectious-Removed (SEIR) epidemic model have enabled a more precise study of the feasibility and efficacy of control measures such as social distancing, work from home, and lockdown, at different moments and stages of the pandemics. Using this model, we study an epidemic outbreak that occurs within densely populated residential areas in Singapore. Our simulations show that residents in densely populated areas could be infected easily, even though they constitute a very small fraction of the whole population. Once infection begins in these areas, disease spreading is uncontrollable if appropriate control measures are not implemented.

The increasing number of accidents arising from falling objects from the façade of tall buildings has attracted much attention globally. To regulators, a preventive approach based on a mandatory periodic façade inspection has been deemed as a necessary measure to maintain the functionality and integrity of the façade of tall buildings. Researchers worldwide have been working towards a predictive approach to allow for the assessment of the likely failure during some future period, by measuring the condition of the façade to detect latent defects and anomalies. The methods proposed include laser scanning, image-based sensing and infrared thermography to support the automatic façade visual inspection. This paper aims to review and analyse the state-of-the-art literature on the automated inspection of building façades, with emphasis on the detection and maintenance management of latent defects and anomalies for falling objects from tall buildings. A step-by-step holistic method is leveraged to retrieve the available literature from databases, followed by the analyses of relevant articles in different long-standing research themes. The types and characteristics of façade falling objects, legislations, practices and the effectiveness of various inspection techniques are discussed. Various diagnostic, inspection and analytical methods which support façade inspection and maintenance are analysed with discussion on the potential future research in this field.

Population-based data on prevalence, causes of blindness and extent of ophthalmological coverage is required for efficient implementation and evaluation of ocular health programs. In view of the scarcity of prevalence data for visual impairment and blindness in Malaysia, this study aims to estimate the prevalence and causes of visual impairment (VI) in the elderly, using Rapid Assessment of Avoidable Blindness (RAAB) survey technique. Malaysia was divided into six regions, with each region consisting of 50 clusters. Multistage cluster sampling method was used and each cluster contained 50 residents aged 50 years and above. Eligible subjects were interviewed and pertinent demographic details, barriers to cataract surgery, medical and ocular history was noted. Subjects had visual acuity assessment with tumbling 'E' Snellen optotypes and ocular examination with direct ophthalmoscope. The primary cause of VI was documented. Results were calculated for individual zones and weighted average was used to obtain overall prevalence for the country. Inter-regional and overall prevalence for blindness, severe VI and moderate VI were determined. Causes of VI, cataract surgical coverage and barriers to cataract surgery were assessed. A total of 15,000 subjects were examined with a response rate of 95.3%. The age and gender-adjusted prevalence of blindness, severe visual impairment and moderate visual impairment were 1.2% (95% Confidence Interval: 1.0-1.4%), 1.0% (95%CI: 0.8-1.2%) and 5.9% (5.3-6.5%) respectively. Untreated cataract (58.6%), diabetic retinopathy (10.4%) and glaucoma (6.6%) were the commonest causes of blindness. Overall, 86.3% of the causes of blindness were avoidable. Cataract surgical coverage (CSC) in persons for blindness, severe visual impairment and moderate visual impairment was 90%, 86% and 66% respectively. Increased patient education and further expansion of ophthalmological services are required to reduce avoidable blindness even further in Malaysia.

The metabolic reprogramming of cancer cells creates metabolic vulnerabilities that can be therapeutically targeted. However, our understanding of metabolic dependencies and the pathway crosstalk that creates these vulnerabilities in cancer cells remains incomplete. Here, by integrating gene expression data with genetic loss-of-function and pharmacological screening data from hundreds of cancer cell lines, we identified metabolic vulnerabilities at the level of pathways rather than individual genes. This approach revealed that metabolic pathway dependencies are highly context-specific such that cancer cells are vulnerable to inhibition of one metabolic pathway only when activity of another metabolic pathway is altered. Notably, we also found that the no single metabolic pathway was universally essential, suggesting that cancer cells are not invariably dependent on any metabolic pathway. In addition, we confirmed that cell culture medium is a major confounding factor for the analysis of metabolic pathway vulnerabilities. Nevertheless, we found robust associations between metabolic pathway activity and sensitivity to clinically approved drugs that were independent of cell culture medium. Lastly, we used parallel integration of pharmacological and genetic dependency data to confidently identify metabolic pathway vulnerabilities. Taken together, this study serves as a comprehensive characterization of the landscape of metabolic pathway vulnerabilities in cancer cell lines.

Key Points A large fraction of point mutations that cause genetic diseases affect splicing efficiency and/or accuracy. Most of these mutations directly affect the canonical consensus sequences that define exon–intron boundaries, and are therefore correctly identified as 'splicing mutations'. Information that is present in the coding regions of genes also contributes to the correct identification of exon–intron boundaries. For example, exonic splicing enhancer (ESE) and silencer (ESS) elements are very prevalent and might be present in most, if not all, constitutive and alternative exons. ESEs are recognized by a class of splicing factors, the SR proteins, that promote splicing by recruiting spliceosomal components to the correct splice sites and/or by antagonizing the action of nearby silencers. Several classes of ESEs, which are recognized by different SR proteins, have been identified, and computational tools are being developed to predict the location, specificity and efficiency of putative ESEs. Because ESEs are embedded in protein-coding sequences, some nonsense, missense and translationally silent point mutations have actually been misclassified. Those mutations that inactivate an ESE can result in partial or complete exon skipping, and can therefore markedly affect the structure or amounts of the expressed protein product. An increasing proportion of point mutations are being reported to affect pre-mRNA splicing. Although reading-frame-dependent mechanisms have been proposed to account for nonsense-associated altered splicing (NAS), in most cases the disruption of ESEs or of RNA secondary structures that are required for proper splicing seems to be the mechanism that leads to exon skipping, regardless of the type of point mutation. Some coding single-nucleotide polymorphisms (cSNPs) can be expected likewise to disrupt elements that are involved in splicing and to exert a subtle effect on splice-site selection, thereby contributing to phenotypic variability, to the variable penetrance of mutations elsewhere in the gene and to cell-type-specific differences in gene expression. The effects of point mutations should be routinely analysed at the mRNA level before drawing conclusions about the importance of the affected amino acid, as their correct classification in terms of the actual mechanism of gene inactivation is essential for understanding structure–function relationships in the corresponding protein, for assessing the phenotypic risk in individuals with familial disease predispositions and for devising new therapies. Point mutations in the coding regions of genes are commonly assumed to exert their effects by altering single amino acids in the encoded proteins. However, there is increasing evidence that many human disease genes harbour exonic mutations that affect pre-mRNA splicing. Nonsense, missense and even translationally silent mutations can inactivate genes by inducing the splicing machinery to skip the mutant exons. Similarly, coding-region single-nucleotide polymorphisms might cause phenotypic variability by influencing splicing accuracy or efficiency. As the splicing mechanisms that depend on exonic signals are elucidated, new therapeutic approaches to treating certain genetic diseases can begin to be explored.

Fish, zooplankton, seston, benthic microalgae and mangrove leaves were examined to investigate the trophic role of zooplankton in the food web of Matang estuaries. Despite the high turbidity and large amounts of detrital material in the water column, the study reveals that phytoplankton fuel the energy flow to zooplankton and small nekton in mangrove-fringed estuaries. The stable carbon isotope (δ13C) values and C/N ratios (7.2 to 8.2) of fine seston (<63 μm) in estuaries indicate the importance of phytoplankton (δ13C: −22.8 ± 0.6‰) to zooplankton (–23.4 to −18.2‰) nutrition, with a trophic contribution of 70 to 84%, whereas mangroves contributed <11%. In adjacent coastal waters, zooplankton (−19.2 to −15.1‰) grazed on both phytoplankton and benthic diatoms (−17.3 ± 1.24‰). Aggregated or mucilage-secreting diatoms (giving depleted δ13C values) were abundant in the estuarine seston, but did not appear to be consumed or assimilated by zooplankton. Stomach content analysis showed significant consumption of zooplankton, especially copepods (mainlyPseudodiaptomus annandalei), sergestids (Acetesspp.) and mysids by young and small nekton (<14 cm standard length) in mangrove estuaries, while δ13C values indicate the increasing importance of mangrove carbon to juvenile fish nutrition (8 to 44%). The range of δ15N values from primary producers to small predatory fish indicates 4 trophic levels (excluding true piscivores) in Matang estuaries, with zooplankton at the second and third trophic level.

In this study, the ternary blends of palm kernel oil (PKO), soybean oil (SBO) and two types of palm stearin (PS) (PS33 and PS38) were systematically prepared and evaluated for their application as an alternative to milk fat in frozen dessert. The physicochemical characteristics namely fatty acids constituent, triacylglycerols (TAGs) composition, melting behavior, solid fat content (SFC) and microstructure were studied. All ternary blends of PKO/SBO/PS33 and PKO/SBO/PS38 had comparable microstructure to that of milk fat. However, 80/15/5 (PKO/SBO/PS33) and 80/15/5 to 80/5/15 (PKO/SBO/PS38) mixtures were found to have similar SFC as milk fat at temperature above 20 °C, allowing these ternary blends to be completely melted at body temperature. With this, 80/15/5 (PKO/SBO/PS33) and 80/15/5 to 80/5/15 (PKO/SBO/PS38) mixtures were able to provide similar meltdown and mouth feel as milk fat at room temperature. Nonetheless, fatty acids constituent, TAGs composition and melting behavior of the blends were different from milk fat. This study showed that ternary blends of PKO, SBO and PS at ratios 80/15/5 (PKO/SBO/PS33) and 80/15/5 to 80/5/15 (PKO/SBO/PS38) can be potentially used as a milk fat alternative for frozen dessert application based on its similar microstructure and SFC profile as the milk fat.

There is considerable need for accurate suicide risk assessment for clinical, screening, and research purposes. This study applied the tripartite affect-behavior-cognition theory, the suicidal barometer model, classical test theory, and item response theory (IRT), to develop a brief self-report measure of suicide risk that is theoretically-grounded, reliable and valid. An initial survey (n = 359) employed an iterative process to an item pool, resulting in the six-item Suicidal Affect-Behavior-Cognition Scale (SABCS). Three additional studies tested the SABCS and a highly endorsed comparison measure. Studies included two online surveys (Ns = 1007, and 713), and one prospective clinical survey (n = 72; Time 2, n = 54). Factor analyses demonstrated SABCS construct validity through unidimensionality. Internal reliability was high (α = .86-.93, split-half = .90-.94)). The scale was predictive of future suicidal behaviors and suicidality (r = .68, .73, respectively), showed convergent validity, and the SABCS-4 demonstrated clinically relevant sensitivity to change. IRT analyses revealed the SABCS captured more information than the comparison measure, and better defined participants at low, moderate, and high risk. The SABCS is the first suicide risk measure to demonstrate no differential item functioning by sex, age, or ethnicity. In all comparisons, the SABCS showed incremental improvements over a highly endorsed scale through stronger predictive ability, reliability, and other properties. The SABCS is in the public domain, with this publication, and is suitable for clinical evaluations, public screening, and research.

Background:Current ultrasound (US) courses focus on the correct and accurate acquisition of images and the identification and scoring of abnormalities rather than how these imaging findings are used in clinical decision making. APLAR Academy considered a new approach to learning through the use of different clinical scenarios and pre- and post- test probability models. Point of care rheumatology ultrasound (POCRUS) as a sensitive and specific prediction tool has gained ground with EULAR recommendations for large vessel vasculitis (LVV) and polymyalgia rheumatica (PMR) criteria.Objectives:Using a POCRUS approach, clinical cases were developed to illustrate how US findings might influence the management of 5 common clinical scenarios - monoarthralgia, oligoarthralgias, small joint polyarthralgias, polymyalgia, or LVV. The course aimed to illustrate and provide a forum for discussion on how POCRUS might facilitate patient management using a clinical, probability-based diagnostic algorithm with the intention of leading to faster and more accurate diagnoses, complementing traditional US teaching.Methods:An online POCRUS course of six sessions was delivered (the first being an introduction to the concept), consisting of lectures on scenarios and case discussions where a novel probability-based model was used. Opportunities were provided for interactions on how POCRUS could be integrated into clinical practice as an adjunct. Pre- and post-course online surveys were undertaken to examine the current US landscape and whether the aims were met post course.Results:Each clinical session consisted of a 45-minute lecture with rotating break-out group case discussions, on how POCRUS as an adjunct to clinical reasoning, can help transition from pre-test to post-test probability of target diagnoses (Figure 1).53/75 (70.7%) attendees completed a pre-course online questionnaire (Table 1). Despite POCRUS availability (81.1%), only 47.2% performed up to 5 scans/month. The main indication was musculoskeletal US (MSUS), with few performing vascular scans. Barriers included time constraints, and lack of training and experience. The vast majority (98.1%) reported that POCRUS may help with diagnosis and management of rheumatic disease by adding to post-test probability.Post-session questionnaires revealed that 93-100% of attendees believed that US would fit well into and add to their clinical practice. The break-out sessions and case-based panel discussions were appreciated as opportunities to ask questions of the expert facilitators and allowed more focus on applying knowledge gained from the prior lecture into practice. 80-93% of attendees reported that their use of US in the subject covered would increase post course. In the vasculitis session 25% reported that the complex imaging procedure was beyond their skill set.Proposed methods to improve learning outcomes and audience participation included pre-selection of participants into basic versus experienced learners. This will enable organizers to stratify the target audience based on US experience. In future, live demonstrations and hands-on teaching could be added.Conclusion:The APLAR scenario-based online education in POCRUS was well received. Almost all reported US added to post-test diagnostic probability and disease management, adding to clinical confidence. POCRUS has potential implications in rheumatology practice for reducing subjective variations in clinical evaluation and diagnostic errors. This should facilitate one-stop consultations for early arthritis or fast-track clinics. POCRUS can represent a major future addition to traditional teaching in rheumatology and ultrasonography with potential in research for formulation and application of predictive diagnostic algorithms.REFERENCES: NILFigure 1.POCRUS probability pathway for gout sequentially applying ACR EULAR gout criteria and sensitive (synovitis)/ specific (double contour, tophi, brightly stippled foci, erosions) ultrasound signs. (a) Synovitis (b) Brightly stippled foci (c) Double contour sign (d) TophiAcknowledgements:We would like to acknowledge the APLAR Academy, APLAR Education Committee and APLAR Secretariat for providing the funding, opportunity, and necessary support to organise and report this Webinar series. We would like to thank Professor Debashish Danda, President of APLAR, and Professor Lai Shan Tam, Convenor APLAR Academy, for their encouragement and support for this course.Disclosure of Interests:None declared.