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In the poorest countries, such as Afghanistan, Haiti, and Mali, the United States has struggled to work with governments whose corruption and lack of capacity are increasingly seen to be the cause of instability and poverty. The development and security communities call for \"good governance\" to improve the rule of law, democratic accountability, and the delivery of public goods and services. The United States and other rich liberal democracies insist that this is the only legitimate model of governance. Yet poor governments cannot afford to govern according to these ideals and instead are compelled to rely more heavily on older, cheaper strategies of holding power, such as patronage and repression. The unwillingness to admit that poor governments do and must govern differently has cost the United States and others inestimable blood and coin. Informed by years of fieldwork and drawing on practitioner work and academic scholarship in politics, economics, law, and history, this book explains the origins of poor governments in the formation of the modern state system and describes the way they govern. It argues that, surprisingly, the effort to stigmatize and criminalize the governance of the poor is both fruitless and destabilizing. The United States must pursue a more effective foreign policy to engage poor governments and acknowledge how they govern.

This dissertation challenges the claims of received Madisonianism that constitutions and law can be auto-implementing through separation of powers and checks and balances. Instead, it argues that law is necessarily endogenously implemented, and that this endogenity has broad implications for how we conceive of the importance of law, the link between law and behavior, the possibility of legal and institutional transfer, and the distinction between law and social norms on the one hand, and law in stateless societies and in societies without states on the other. Endogenous legal implementation leads us to conceive of a different systemic view of law, in which actors, not rules, are the subparts, and they interrelate, not through the rules of predicate logic, but by the impact they have on each other's implementation decisions. Investigating Madisonian mechanisms of accountability in the newly democratized Republic of Mali, this dissertation rejects inter-branch equilibrium notions and argue that internal executive policing is at the heart of legal implementation, not just in Mali, but in all three-branch constitutional democracies.

Heatwaves have implications for human health and ecosystem function. Over cities, the impacts of a heatwave event may be compounded by urban heat, where temperatures over the urban area are higher than their rural surroundings. Coastal cities often rely upon sea breezes to provide temporary relief. However, topographic features contributing to the development of Foehn-like conditions can offset the cooling influence of sea breezes. Using convection-permitting simulations (⩽4 km) we examine the potential for both mechanisms to influence heatwave conditions over the large coastal city of Sydney, Australia that is bordered by mountains. Heatwave onset in the hot period of January–February 2017 often coincides with a hot continental flow over the mountains into the city. The temperature difference between the coast and the urban–rural interface can reach 15.79 °C. Further, the urban heat island contributes on average an additional 1 °C in the lowest 1 km of the atmosphere and this often extends beyond the city limits. The cumulative heat induced by the urban environment reaches 10 °C over the city and 3 °C over adjacent inland areas. Strong sea breezes are important for heat dispersion with city temperature gradients reducing to within 1 °C. The resolution permits a comparison between urban types and reveals that the diurnal cycle of temperature, moisture content and wind are sensitive to the urban type. Here we show that convection permitting simulations can resolve the interaction between local breezes and the urban environment that are not currently resolved in coarser resolution models.

Multiple stringent confinement strategies should be used whenever possible Gene drive systems promote the spread of genetic elements through populations by assuring they are inherited more often than Mendelian segregation would predict (see the figure). Natural examples of gene drive from Drosophila include sex-ratio meiotic drive, segregation distortion, and replicative transposition. Synthetic drive systems based on selective embryonic lethality or homing endonucleases have been described previously in Drosophila melanogaster ( 1 – 3 ), but they are difficult to build or are limited to transgenic populations. In contrast, RNAguided gene drives based on the CRISPR/Cas9 nuclease can, in principle, be constructed by any laboratory capable of making transgenic organisms ( 4 ). They have tremendous potential to address global problems in health, agriculture, and conservation, but their capacity to alter wild populations outside the laboratory demands caution ( 4 – 7 ). Just as researchers working with self-propagating pathogens must ensure that these agents do not escape to the outside world, scientists working in the laboratory with gene drive constructs are responsible for keeping them confined ( 4 , 6 , 7 ).

The eighth meeting of the International Collaboration for the Automation of Systematic Reviews (ICASR) was held on September 7 and 8, 2023, at the University College London, London, England. ICASR is an interdisciplinary group whose goal is to maximize the use of technology for conducting rapid, accurate, and efficient evidence synthesis, e.g., systematic reviews, evidence maps, and scoping reviews of scientific evidence. In 2023, the major themes discussed were understanding the benefits and harms of automation tools that have become available in recent years, the advantages and disadvantages of large language models in evidence synthesis, and approaches to ensuring the validity of tools for the proposed task.

BackgroundCemiplimab, a high-affinity, potent human immunoglobulin G4 monoclonal antibody to programmed cell death-1 demonstrated antitumor activity in a Phase 1 advanced cutaneous squamous cell carcinoma (CSCC) expansion cohort (NCT02383212) and the pivotal Phase 2 study (NCT02760498). Here we report the primary analysis of fixed dose cemiplimab 350 mg intravenously every 3 weeks (Q3W) (Group 3) and provide a longer-term update after the primary analysis of weight-based cemiplimab 3 mg/kg intravenously every 2 weeks (Q2W) (Group 1) among metastatic CSCC (mCSCC) patients in the pivotal study (NCT02760498).MethodsThe primary objective for each group was objective response rate (ORR) per independent central review (ICR). Secondary endpoints included ORR by investigator review (INV), duration of response (DOR) per ICR and INV, and safety and tolerability.ResultsFor Group 3 (n=56) and Group 1 (n=59), median follow-up was 8.1 (range, 0.6 to 14.1) and 16.5 (range, 1.1 to 26.6) months, respectively. ORR per ICR was 41.1% (95% CI, 28.1% to 55.0%) in Group 3, 49.2% (95% CI, 35.9% to 62.5%) in Group 1, and 45.2% (95% CI, 35.9% to 54.8%) in both groups combined. Per ICR, Kaplan–Meier estimate for DOR at 8 months was 95.0% (95% CI, 69.5% to 99. 3%) in responding patients in Group 3, and at 12 months was 88.9% (95% CI, 69.3% to 96.3%) in responding patients in Group 1. Per INV, ORR was 51.8% (95% CI, 38.0% to 65.3%) in Group 3, 49.2% (95% CI, 35.9% to 62.5%) in Group 1, and 50.4% (95% CI, 41.0% to 59.9%) in both groups combined. Overall, the most common adverse events regardless of attribution were fatigue (27.0%) and diarrhea (23.5%).ConclusionIn patients with mCSCC, cemiplimab 350 mg intravenously Q3W produced substantial antitumor activity with durable response and an acceptable safety profile. Follow-up data of cemiplimab 3 mg/kg intravenously Q2W demonstrate ongoing durability of responses.Trial registration numberClinicaltrials.gov, NCT02760498. Registered May 3, 2016, https://clinicaltrials.gov/ct2/show/NCT02760498

Obesity in pregnancy may negatively influence maternal and infant iron status. The aim of this study was to examine the association of obesity with inflammatory and iron status in both mother and infant in two prospective studies in pregnancy: UPBEAT and SCOPE. Maternal blood samples from obese (n = 245, BMI ≥ 30 kg/m2) and normal weight (n = 245, BMI < 25 kg/m2) age matched pregnant women collected at approximately 15 weeks’ gestation, and umbilical cord blood samples collected at delivery, were analysed for a range of inflammatory and iron status biomarkers. Concentrations of C- reactive protein and Interleukin-6 in obese women compared to normal weight women were indicative of an inflammatory response. Soluble transferrin receptor (sTfR) concentration [18.37 nmol/L (SD 5.65) vs. 13.15 nmol/L (SD 2.33)] and the ratio of sTfR and serum ferritin [1.03 (SD 0.56) vs. 0.69 (SD 0.23)] were significantly higher in obese women compared to normal weight women (P < 0.001). Women from ethnic minority groups (n = 64) had higher sTfR concentration compared with white women. There was no difference in maternal hepcidin between obese and normal weight women. Iron status determined by cord ferritin was not statistically different in neonates born to obese women compared with neonates born to normal weight women when adjusted for potential confounding variables. Obesity is negatively associated with markers of maternal iron status, with ethnic minority women having poorer iron statuses than white women.

Background There is growing evidence that context mediates the effects of implementation interventions intended to increase healthcare professionals’ use of research evidence in clinical practice. However, conceptual clarity about what comprises context is elusive. The purpose of this study was to advance conceptual clarity on context by developing the Implementation in Context Framework, a meta-framework of the context domains, attributes and features that can facilitate or hinder healthcare professionals’ use of research evidence and the effectiveness of implementation interventions in clinical practice. Methods We conducted a meta-synthesis of data from three interrelated studies: (1) a concept analysis of published literature on context ( n  = 70 studies), (2) a secondary analysis of healthcare professional interviews ( n  = 145) examining context across 11 unique studies and (3) a descriptive qualitative study comprised of interviews with heath system stakeholders ( n  = 39) in four countries to elicit their tacit knowledge on the attributes and features of context. A rigorous protocol was followed for the meta-synthesis, resulting in development of the Implementation in Context Framework. Following this meta-synthesis, the framework was further refined through feedback from experts in context and implementation science. Results In the Implementation in Context Framework, context is conceptualized in three levels: micro (individual), meso (organizational), and macro (external). The three levels are composed of six contextual domains: (1) actors (micro), (2) organizational climate and structures (meso), (3) organizational social behaviour (meso), (4) organizational response to change (meso), (5) organizational processes (meso) and (6) external influences (macro). These six domains contain 22 core attributes of context and 108 features that illustrate these attributes. Conclusions The Implementation in Context Framework is the only meta-framework of context available to guide implementation efforts of healthcare professionals. It provides a comprehensive and critically needed understanding of the context domains, attributes and features relevant to healthcare professionals’ use of research evidence in clinical practice. The Implementation in Context Framework can inform implementation intervention design and delivery to better interpret the effects of implementation interventions, and pragmatically guide implementation efforts that enhance evidence uptake and sustainability by healthcare professionals.