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Abstract Background The treatment of children with multisystem inflammatory syndrome in children (MIS-C) related to SARS-CoV-2 infection involves immunomodulatory therapies such as IVIG and steroids. Anakinra, an interleukin-1 receptor inhibitor, has also been used, but its effectiveness is not established yet. As optimal regimens for MIS-C remain unknown, we aimed to assess the effect of anakinra in reducing hospital stay in patients with MIS-C. Methods We included children admitted from May 2020 to May 2021 diagnosed with MIS-C based on CDC criteria. The exposure of interest was anakinra use at any point during admission. The anakinra exposed group and the anakinra unexposed group were propensity score matched based on demographic and clinical severity indicators at initial presentation. Our primary outcome was length of hospital stay. Secondary outcomes were duration of vasoactive support, vasoactive inotropic score (VIS), level of respiratory support, time to fever resolution, reduction of CRP levels, and length of ICU stay. We used Wilcoxon rank sum, t-test, Chi square and Fisher’s exact tests. Results Of 138 children diagnosed with MIS-C, 79% had moderate or severe illness and 41% received anakinra. Of those, 31 patients who received anakinra were propensity score matched to 31 who did not. The length of stay in the hospital but not in the ICU was longer in the anakinra group. There were no differences in median duration of vasoactive support, fever resolution, CRP reduction, or VIS. Conclusions In patients with moderate to severe MIS-C, use of anakinra was associated with longer duration of hospital stay.

Abstract A major goal of biological control is the reduction and/or eradication of pests using various natural enemies, in particular, via deliberate infection of the target species by parasites. To enhance the biological control, a promising strategy seems to implement a multi-enemy assemblage rather than a single control agent. Although a large body of theoretical studies exists on co-infections in epidemiology and ecology, there is still a big gap in modelling outcomes of multi-enemy biological control. Here we theoretically investigate how the efficiency of biological control of a pest depends on the number of natural enemies used. We implement a combination of eco-epidemiological modelling and the Adaptive Dynamics game theory framework. We found that a progressive addition of parasite species increases the evolutionarily stable virulence of each parasite, and thus enhances the mortality of the target pest. However, using multiple enemies may have only a marginal effect on the success of biological control, or can even be counter-productive when the number of enemies is excessive. We found the possibility of evolutionary suicide, where one or several parasite species go extinct over the course of evolution. Finally, we demonstrate an interesting scenario of coexistence of multiple parasites at the edge of extinction.

Objective: The Surgical Training and Educational Platform (STEP) was developed by the American Society for Surgery of the Hand (ASSH) as a cost-effective set of surgical simulation modules designed to represent critical psychomotor skills in hand surgery. We hypothesize that increased training on these training modules, even with limited supervision, would improve resident performance on psychomotor skills. Design: Baseline evaluation was conducted on four psychomotor skills to simulate surgical tasks: lag screw fixation, depth of plunge, skin graft harvest, and wrist arthroscopy. One-third of them received limited supervised training for one month and two-thirds did not (control). After the training period both groups were re-evaluated and their performance was analysed. Setting: Six ACGME accredited orthopaedic surgery residency programs. Participants: All 26 residents in the intern bootcamp participated and completed the study. Selection to the Trained Group was based on willingness and ability to participate. Others remained in the Control Croup. Results: Compared to baseline, the Control Group performed worse in depth of plunge while showing no improvement in other tasks in the final assessment. Compared to baseline, the Trained Group improved in lag screw fixation and in total score after training, with the greatest improvement in the half with the lowest pre-training scores. Post-training, the Trained Group outperformed the Control Group in depth of plunge. Conclusions: Training outside the operating room even with limited supervision improved psychomotor skills in orthopaedic surgery interns as assessed by the STEP modules. The STEP simulator is a validated instrument and may be valuable for resident education and assessment.

Abstract Background Patients with axial spondyloarthritis (axSpA) may experience spinal stiffness and pain, leading to reduced physical function and quality of life. Despite the benefits of physical activity (PA) and exercise, previous studies have demonstrated lower levels of PA among patients with axSpA. This study aims to examine the patterns of PA among patients with axSpA compared to the general population in a multi-ethnic Asian country. Methods This was a cross-sectional study conducted between May 2016 and Jan 2017. Consecutive patients with axSpA were recruited at an outpatient rheumatology clinic at Singapore General Hospital, the largest tertiary hospital in Singapore. Controls were based on a previous cross-sectional study. PA was assessed using the Global Physical Activity Questionnaire (GPAQ). Results Seventy-four patients with axSpA were recruited and compared with 2679 controls. Lower proportion of patients with axSpA met the WHO recommendations for PA (axSpA = 77.0%, controls = 89.7%, p

Abstract We apply mathematical modelling to explore bacteria-phage interaction mediated by condition-dependent lysogeny, where the type of the phage infection cycle (lytic or lysogenic) is determined by the ambient temperature. In a natural environment, daily and seasonal variations of the temperature cause a frequent switch between the two infection scenarios, making the bacteria-phage interaction with condition-dependent lysogeny highly complex. As a case study, we explore the natural control of the pathogenic bacteria Burkholderia pseudomallei by its dominant phage. B. pseudomallei is the causative agent of melioidosis, which is among the most fatal diseases in Southeast Asia and across the world. We assess the spatial aspect of B. pseudomallei-phage interactions in soil, which has been so far overlooked in the literature, using the reaction-diffusion PDE-based framework with external forcing through daily and seasonal parameter variation. Through extensive computer simulations for realistic biological parameters, we obtain results suggesting that phages may regulate B. pseudomallei numbers across seasons in endemic areas, and that the abundance of highly pathogenic phage-free bacteria shows a clear annual cycle. The model predicts particularly dangerous soil layers characterised by high pathogen densities. Our findings can potentially help refine melioidosis prevention and monitoring practices.

As a public space and building, the footbridge is not just a physical concrete building but also carries people’s life experiences and beliefs. In Hong Kong, however, footbridges are a joint product of the government and property developers to control people and drive consumption. Taking the footbridge as an example, this article explores the relationship between public space and the power of discourse. The article first discusses how the government and property developers manipulate footbridges as a social control tool. This article draws on case studies of the use of public space during and after Hong Kong’s social movements in 2019 to discuss how people tried to regain their power of discourse in urban space, and how the government and the bourgeoisie suppressed such attempts. This paper argues that footbridges serve as marginal spaces, and demonstrate power and control by providing a space for people to discuss public affairs and be used to demonstrate power and control, especially in social movements. The footbridges traditionally used are challenged in a social event at the same time, brought under the gaze of planning and management from authorities, on the meaning of public space, the footbridges are narrowed or even prohibited in Hong Kong.

Campylobacter jejuni (C. jejuni) causes gastroenteritis following the consumption of contaminated poultry meat, resulting in a large health and economic burden worldwide. Phage therapy is a promising technique for eradicating C. jejuni from poultry flocks and chicken carcasses. However, C. jejuni can resist infections by some phages through stochastic, phase-variable ON/OFF switching of the phage receptors mediated by simple sequence repeats (SSR). While selection strength and exposure time influence the evolution of SSR-mediated phase variation (PV), phages offer a more complex evolutionary environment as phage replication depends on having a permissive host organism. Here, we build and explore several continuous culture bacteria-phage computational models, each analysing different phase-variable scenarios calibrated to the experimental SSR rates of C. jejuni loci and replication parameters for the F336 phage. We simulate the evolution of PV rates via the adaptive dynamics framework for varying levels of selective pressures that act on the phage-resistant state. Our results indicate that growth reducing counter-selection on a single PV locus results in the stable maintenance of the phage, while compensatory selection between bacterial states affects the evolutionary stable mutation rates (i.e. very high and very low mutation rates are evolutionarily disadvantageous), whereas, in the absence of either selective pressure the evolution of PV rates results in mutation rates below the basal values. Contrastingly, a biologically-relevant model with two phase-variable loci resulted in phage extinction and locking of the bacteria into a phage-resistant state suggesting that another counter-selective pressure is required, instance, the use of a distinct phage whose receptor is an F336-phage-resistant state. We conclude that a delicate balance between counter-selection and phage-attack can result in both the evolution of phase-variable phage receptors and persistence of PV-receptor-specific phage.

Understanding CRISPR-Cas systems-the adaptive defence mechanism that about half of bacterial species and most of archaea use to neutralise viral attacks-is important for explaining the biodiversity observed in the microbial world as well as for editing animal and plant genomes effectively. The CRISPR-Cas system learns from previous viral infections and integrates small pieces from phage genomes called spacers into the microbial genome. The resulting library of spacers collected in CRISPR arrays is then compared with the DNA of potential invaders. One of the most intriguing and least well understood questions about CRISPR-Cas systems is the distribution of spacers across the microbial population. Here, using empirical data, we show that the global distribution of spacer numbers in CRISPR arrays across multiple biomes worldwide typically exhibits scale-invariant power law behaviour, and the standard deviation is greater than the sample mean. We develop a mathematical model of spacer loss and acquisition dynamics which fits observed data from almost four thousand metagenomes well. In analogy to the classical 'rich-get-richer' mechanism of power law emergence, the rate of spacer acquisition is proportional to the CRISPR array size, which allows a small proportion of CRISPRs within the population to possess a significant number of spacers. Our study provides an alternative explanation for the rarity of all-resistant super microbes in nature and why proliferation of phages can be highly successful despite the effectiveness of CRISPR-Cas systems.

(1) Background: Hong Kong is experiencing population aging, but there is little research on advance care planning. This research asks for community-dwelling older adults’ views on advance care planning in order to provide a different angle to the results collected from nursing homes and hospitals. (2) Methods: The targeted respondents were people aged 55 or above. A total of 282 questionnaires were collected using the random sampling method. Respondents were asked whether they would make an advance care plan, whether they would prepare for their death, and whether they had received any death education; they were also given eight statements related to treatments and decision making. (3) Results: The study found that only 17% of the respondents would like to use advance care planning, even after it was explained to them. Advance care planning favorers would be more likely to insist on having wills and would be more likely to trust doctors rather than family members. (4) Conclusions: The results also suggested that the medical care and social support for end-of-life patients should be improved. The results also showed the importance of medical professionals as they showed that respondents wanted advice on end-of-life decision-making from medical professionals.