The Physics of the B Factories

This work is on the Physics of the B Factories. Part A of this book contains a brief description of the SLAC and KEK B Factories as well as their detectors, BaBar and Belle, and data taking related issues. Part B discusses tools and methods used by the experiments in order to obtain results. The results themselves can be found in Part C

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Development of a cell-free DNA methodology to assess organ rejection after liver transplantation

© 2019 Su Kah GohBackground: Liver transplantation has revolutionised the prognosis of patients with fulminant liver failure, chronic liver disease, and liver cancer. Although liver transplantation is safe, organ rejection is a common complication after such a procedure. The gold-standard for diagnosing organ rejection after liver transplantation is a tissue biopsy. Liver biopsies are invasive. There is thus an unmet clinical need for accurate blood tests to diagnose the episodes of organ rejection after liver transplantation. Donor-specific cell-free DNA (dscfDNA) is an emerging biomarker of organ rejection. Measuring dscfDNA using current methodologies such as next generation sequencing can be both complex and expensive. Novel tests that overcome these limitations would favour adoption of such methodologies for the quantification of dscfDNA and implementation for the surveillance of organ rejection after transplantation. Objectives: The first objective of this thesis was to develop a cell-free DNA based assay for the accurate quantification of dscfDNA that could overcome some of the limitations of existing methodologies. The second objective of this thesis was to deploy this assay to monitor episodes of organ rejection in a prospective cohort of recipients. Main findings: A probe-free droplet digital PCR-based methodology was developed. The methodology overcame some of the common limitations that were observed in next generation sequencing-based and other PCR-based methodologies. The newly developed approach was accurate, economical, and rapid which facilitated the rapid turnaround of results as well as enabled early clinical decision-making (Chapters 3 and 4). The application of this approach to measure dscfDNA was shown to be feasible for the monitoring of dscfDNA in a prospective cohort of forty recipients after liver transplantation (Chapter 5). The levels of dscfDNA were reflective of organ health. Furthermore, a calculated threshold of 898 copies of dscfDNA per mL of recipient plasma identified majority of the recipients with biopsy-proven acute rejection requiring treatment. The diagnostic performance of dscfDNA, in this cohort, was superior compared to routine liver function tests in identifying organ rejection. Conclusion: This thesis presented the application of a novel cfDNA methodology to measure dscfDNA in a prospective cohort of recipients after liver transplantation. The results demonstrated the promising utility of dscfDNA as a marker of organ rejection after liver transplantation. These pertinent findings warrant further validation with a view towards clinical implementation

Investigation of inerter-based suspension systems for heavy vehicles.

The inerter is a two-terminal component that can be added to the spring-and-damper configuration of a suspension system. It has the property that the force exerted is proportional to the relative acceleration at its terminals. Studies have demonstrated the inerter's benefit of providing superior vibration isolation when it is used in the vehicle suspension of passenger cars. However, similar benefit on another common vehicle class on the roads, namely heavy vehicles, remain to be shown, as these vehicles have vastly different parameter values than passenger cars. This study is an investigation on the performance improvement brought by an inerter in the suspension of common heavy vehicles. In the study, the parameter values of a truck and a bus were adopted in the quarter vehicle model with two different spring-damper-inerter configurations (parallel and serial inerter), and the improvements in vibration isolation and road holding capability were determined by optimization of inertance. Results show that the inerter is similarly effective in providing the said improvements when implemented on heavy vehicles instead of on passenger cars, judging from reductions in sprung mass acceleration and dynamic tire load. It is also observed that the performance benefit is associated with larger optimum inertance than that for passenger cars. Overall, the inerter has been shown to be beneficial in the parallel and serial configurations, both of which are common and can be practically implemented in the suspension of heavy vehicles

Circulating Biomarkers for Prediction of Immunotherapy Response in NSCLC

Non-small cell lung cancer (NSCLC) constitutes the majority of the lung cancer population and the prognosis is poor. In recent years, immunotherapy has become the standard of care for advanced NSCLC patients as numerous trials demonstrated that immune checkpoint inhibitors (ICI) are more efficacious than conventional chemotherapy. However, only a minority of NSCLC patients benefit from this treatment. Therefore, there is an unmet need for biomarkers that could accurately predict response to immunotherapy. Liquid biopsy allows repeated sampling of blood-based biomarkers in a non-invasive manner for the dynamic monitoring of treatment response. In this review, we summarize the efforts and progress made in the identification of circulating biomarkers that predict immunotherapy benefit for NSCLC patients. We also discuss the challenges with future implementation of circulating biomarkers into clinical practice

Evaluating DNA recovery efficiency following bisulphite modification from plasma samples submitted for cell-free DNA methylation analysis

The detection of methylated templates in cell-free DNA (cfDNA) is increasingly recognized as a valuable, non-invasive tool for diagnosis, monitoring and prognostication in a range of medical contexts. The importance of controlling pre-analytical conditions in laboratory workflows prior to cfDNA quantification is well-established. Significant variations in the recovery of DNA following processes such as cfDNA extraction and sodium bisulphite modification may confound downstream analysis, particularly when accurate quantification of templates is required. Given the wealth of potential applications for this emerging molecular technology, attention has turned to the requirement to recognize and minimize pre-analytical variables prior to cfDNA methylation analysis. We recently described the development of an approach using an exogenous DNA construct to evaluate the recovery efficiency of cfDNA following the extraction and bisulphite modification steps (CEREBIS). Here, we report our experience in the practical application of this technique in 107 consecutive patient plasma samples submitted for quantitative cfDNA methylation analysis. The mean recovery of cfDNA (as estimated using cerebis), following extraction and bisulphite modification, was 37% ± 7%. Nine (8.4%) of the 107 samples were found to be outside of control limits, where the recovery of cerebis indicated significant differences in the efficiency of the pre-analytical processing of these samples. Recognition of these out-of-control samples precluded subsequent molecular analysis. Implementation of data-driven quality control measures, such as the one described, has the potential to improve the quality of liquid biopsy methylation analysis, interpretation and reporting

Psychological impact of repeated epidemic exposure on healthcare workers: findings from an online survey of a healthcare workforce exposed to both SARS (severe acute respiratory syndrome) and COVID-19

Objective: To measure the psychological well-being of healthcare workers (HCWs) during this COVID-19 pandemic and examine the experiences of the subgroup of participants who were also HCWs during the 2003 SARS epidemic. Design: Anonymous online survey adapted from a similar study conducted during the SARS epidemic, disseminated from July 2020 to August 2020. Setting: Nine healthcare institutions across Singapore ranging from primary care, community care, tertiary care and specialised referral centres. Participants: Employees working in the participating healthcare institutions. Results: Of 3828 survey returns, 3616 had at least one completed item on the questionnaire. Majority were female (74.7%), nurses (51.7%), foreign-born (53.2%) and not working in the tertiary care setting (52.1%). The median score on the Impact of Events Scale (IES) was 15 (IQR 23) and 28.2% of the sample scored in the moderate/severe range. 22.7% of the participants were also HCWs during SARS and more than half of them felt safer and better equipped in the current pandemic. 25.2% of SARS HCWs and 25.9% of non-SARS HCWs had moderate/severe IES scores (p=0.904). After adjusting for age, marital status, parity and length of work experience, racial minority groups and living apart from family were independent predictors of high IES regardless of prior SARS epidemic experience. Daily exposure to confirmed or suspect COVID-19 cases increased the odds of high IES for nonSARS HCWs only. Conclusions and relevance: Overall, while 28% of HCWs in our study suffered from significant trauma-related psychological symptoms regardless of prior experience with the SARS epidemic, those with prior experience reported feeling safer and better equipped, finding the workload easier to manage, as well as having more confidence in their healthcare leaders. We recommend for more trauma-informed support strategies for our HCWs especially those from racial minority groups, who are foreign-born and isolated from their families.Published versio

Association of Country Income Level With the Characteristics and Outcomes of Critically Ill Patients Hospitalized With Acute Kidney Injury and COVID-19

Introduction: Acute kidney injury (AKI) has been identified as one of the most common and significant problems in hospitalized patients with COVID-19. However, studies examining the relationship between COVID-19 and AKI in low- and low-middle income countries (LLMIC) are lacking. Given that AKI is known to carry a higher mortality rate in these countries, it is important to understand differences in this population. Methods: This prospective, observational study examines the AKI incidence and characteristics of 32,210 patients with COVID-19 from 49 countries across all income levels who were admitted to an intensive care unit during their hospital stay. Results: Among patients with COVID-19 admitted to the intensive care unit, AKI incidence was highest in patients in LLMIC, followed by patients in upper-middle income countries (UMIC) and high-income countries (HIC) (53%, 38%, and 30%, respectively), whereas dialysis rates were lowest among patients with AKI from LLMIC and highest among those from HIC (27% vs. 45%). Patients with AKI in LLMIC had the largest proportion of community-acquired AKI (CA-AKI) and highest rate of in-hospital death (79% vs. 54% in HIC and 66% in UMIC). The association between AKI, being from LLMIC and in-hospital death persisted even after adjusting for disease severity. Conclusions: AKI is a particularly devastating complication of COVID-19 among patients from poorer nations where the gaps in accessibility and quality of healthcare delivery have a major impact on patient outcomes