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The global crisis of antimicrobial resistance (AMR) necessitates the development of broad-spectrum antibacterial drugs effective against multi-drug resistant (MDR) pathogens. BWC0977, a Novel Bacterial Topoisomerase Inhibitor (NBTI) selectively inhibits bacterial DNA replication via inhibition of DNA gyrase and topoisomerase IV. BWC0977 exhibited a minimum inhibitory concentration (MIC 90 ) of 0.03–2 µg/mL against a global panel of MDR Gram-negative bacteria including Enterobacterales and non-fermenters, Gram-positive bacteria, anaerobes and biothreat pathogens. BWC0977 retains activity against isolates resistant to fluoroquinolones (FQs), carbapenems and colistin and demonstrates efficacy against multiple pathogens in two rodent species with significantly higher drug levels in the epithelial lining fluid of infected lungs. In healthy volunteers, single-ascending doses of BWC0977 administered intravenously ( https://clinicaltrials.gov/study/NCT05088421 ) was found to be safe, well tolerated (primary endpoint) and achieved dose-proportional exposures (secondary endpoint) consistent with modelled data from preclinical studies. Here, we show that BWC0977 has the potential to treat a range of critical-care infections including MDR bacterial pneumonias. In this work, the authors probe the efficacy of BWC0977, a bacterial topoisomerase inhibitor, in pre-clinical animal models, also demonstrating that BWC0977 is safe and well tolerated in healthy human volunteers, in a phase 1 trial.

\"In Moulmein, in Lower Burma, I was hated by large numbers of people ...\" So begins one of Orwell's most famous essays. In Orwell: The Road to Airstrip One Ian Slater explains why Orwell was hated in Moulmein and takes us on a fascinating intellectual journey that traces the development of Orwell's political and social criticism. Using a uniquely thematic approach, Slater also examines Orwell's self-criticism and, finally, the hidden and corrosive dangers of state and self-imposed censorship in a security-obsessed world. Slater's tour de force, critically acclaimed by those on both the left and the right, moves from Orwell's schooldays in England and his time as a policeman in Burma, through his years as a struggling poet, dishwasher, tramp in Paris, and tutor, schoolmaster, and bookshop assistant in London, to his critical experiences during the Spanish Civil War. Slater takes us beyond the events of Orwell's life to the bitter satire of the Russian Revolution in Animal Farm and the horrifying terror of Room 101 in 1984, Orwell's final novel, and shows that 1984 is as much a warning about the state of mind we call totalitarianism as it is a prophecy of an actual political state. As the war on terrorism continues and governments demand ever-increasing power over the individual in order to combat terrorism, Orwell: The Road to Airstrip One, reissued during Orwell's centenary, warns us that \"he who fights with monsters should be careful lest he thereby become a monster.\"

Atomic Energy Canada Limited pursued the development of a small-scale nuclear reactor intended for use in the North Warning System during the height of the Cold War. This reactor, known as the nuclear battery, was later considered as a submarine power source for the Canadian Submarine Acquisition Program (CASAP). AECL’s approach to the development of the nuclear battery was to form joint-venture partnerships with public- and private-sector companies in order to share design and development costs; however, AECL had both the funding and the in-house technical and scientific expertise to develop the nuclear battery without these partnerships. Further, the pursuit of these partnerships did not lead to success; the nuclear battery was a failed innovation. This study links the preference for joint-venture partnerships at AECL to the neo-liberal approach to innovation that swept through Canadian government and private-sector industries in the 1980s and early 1990s, as it had swept through British and American industries before it.

\"In Moulmein, in Lower Burma, I was hated by large numbers of people ...\" So begins one of Orwell's most famous essays. In Orwell: The Road to Airstrip One Ian Slater explains why Orwell was hated in Moulmein and takes us on a fascinating intellectual journey that traces the development of Orwell's political and social criticism. Using a uniquely thematic approach, Slater also examines Orwell's self-criticism and, finally, the hidden and corrosive dangers of state and self-imposed censorship in a security-obsessed world. Slater's tour de force, critically acclaimed by those on both the left and the right, moves from Orwell's schooldays in England and his time as a policeman in Burma, through his years as a struggling poet, dishwasher, tramp in Paris, and tutor, schoolmaster, and bookshop assistant in London, to his critical experiences during the Spanish Civil War. Slater takes us beyond the events of Orwell's life to the bitter satire of the Russian Revolution in Animal Farm and the horrifying terror of Room 101 in 1984, Orwell's final novel, and shows that 1984 is as much a warning about the state of mind we call totalitarianism as it is a prophecy of an actual political state. As the war on terrorism continues and governments demand ever-increasing power over the individual in order to combat terrorism, Orwell: The Road to Airstrip One, reissued during Orwell's centenary, warns us that \"he who fights with monsters should be careful lest he thereby become a monster.\"

The college experiences of lesbian, gay, bisexual, transgender, and queer (LGBTQ+) students in U.S. higher education have been characterized by bullying, harassment, and feelings of rejection or alienation (Rankin, Weber, Blumenfeld, & Frazer, 2010). These negative experiences often contribute to poor psychological health and success outcomes in college. LGBTQ+ students attending U.S. Christian colleges and universities face additional challenges when pursuing their educational goals due, in great part, to the effects of theological convictions about human sexuality and gender on campus culture, policies, and behaviors. Prior studies have described a need for quantitative research to advance an understanding of the relationships between various campus experiences and positive college outcomes for LGBTQ+ students. This study thus examined the contributions of student characteristics and college experiences on student thriving, a holistic measure of success that incorporates dimensions of academic, psychological, and interpersonal flourishing (Schreiner, 2016). Data were collected as a part of a national study on college student thriving, and the final dataset included 293 LGBTQ+ undergraduate students from 15 member institutions of the Council for Christian Colleges & Universities (CCCU). Structural equation modeling (SEM) was utilized to explore the relationships between variables and identify their direct, indirect, and total effects on student thriving. The final structural regression model for LGBTQ+ students explained 53% of the variance in student thriving and demonstrated acceptable fit to the data (χ2 (213) = 391.99; p <.001; CFI = .920; RMSEA = .054). Psychological sense of community, institutional integrity, spirituality, student-faculty interaction, faculty sensitivity to diverse perspectives and viewpoints in class, and feelings of acceptance on campus represented key contributors to LGBTQ+ student thriving. This study provides recommendations to address negative aspects of the campus climate, foster transformational experiences, and cultivate supportive relationships and spaces of belonging for LGBTQ+ students.

For decades, mathematicians and statisticians have been modelling infectious diseases to forecast case/death counts, estimate important epidemiological quantities, and understand the dynamics of disease spread. This dissertation offers methodological insights into each of these three challenges using novel spatial, spatio-temporal, and Bayesian modelling methods, with applications to COVID-19 data. Alongside methodological contributions, this thesis also presents estimates of important epidemiological quantities which, subject to peer review, could be utilized by public health professionals and policy makers. There are four primary contributions of this work: 1) a subnational, single-wave COVID-19 mortality forecasting model that accounts for day-of-the-week effects, which was shown to outperform the most highly-cited model during the first viral wave; 2) a mobility-augmented spatial model for COVID-19 case counts, where cellphone-derived mobility data is shown to capture dependence between areal units better than physical proximity; 3) a novel, interpretable spatio-temporal infectious disease model where infectiousness is a function of mobility between areal units, resulting in estimates of the risk associated with travelling in two Spanish Communities; 4) a modular Bayesian framework based on mixture modelling of serological data and disaggregated deaths data to estimate COVID-19 incidence and infection fatality rates, resulting in estimates of these quantities across Canada for various strata. Although the applications in this thesis are to COVID-19 data, the proposed methodology can be applied to a wide spectrum of problems across infectious disease epidemiology.

Eric Scerri has argued that chemists using ab initio calculations pursue a partial reduction of chemistry to physics, while accepting that full reduction (through axiomatization) is impractical. He characterizes this view as Popperian and naturalistic. However, Popper's position on reduction is not naturalistic, as he rejected axiomatization for different reasons.