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Over the past 5 years, advanced assisted reproductive technologies (ARTs), such as mitochondrial replacement therapies (MRTs) and heritable human genome editing (HHGE), have raised global policy concerns and fears of 'unregulated' proliferation. Yet, few innovations are ever truly unregulated and more often fall within the scope of one or more pre-existing regulatory regimes, a process referred to as 'inherited regulation'. While the United Kingdom has enacted new legislation to specifically authorize and closely regulate MRTs, many jurisdictions will likely default to current oversight systems to manage advanced ARTs. This article evaluates and compares how several jurisdictions have already used four types of inherited regulatory regimes to manage MRTs and HHGE. Cases are drawn from jurisdictions where inherited regulatory interventions on advanced ARTs have taken place (USA, Greece, Ukraine, China, and Russia) and include jurisdictions closely connected with those cases (Mexico and Spain). When accounting for political, cultural, and religious contexts, many of these inherited regimes offer promise as starting points for governance of advanced ARTs, yet each will require further adjustments and tailoring to adequately manage the benefits and risks of these powerful innovations., (© The Author(s) 2022. Published by Oxford University Press on behalf of Duke University School of Law, Harvard Law School, Oxford University Press, and Stanford Law School.)

Wildland fire management has reached a crossroads. Current perspectives are not capable of answering interdisciplinary adaptation and mitigation challenges posed by increases in wildfire risk to human populations and the need to reintegrate fire as a vital landscape process. Fire science has been, and continues to be, performed in isolated "silos," including institutions (e.g., agencies versus universities), organizational structures (e.g., federal agency mandates versus local and state procedures for responding to fire), and research foci (e.g., physical science, natural science, and social science). These silos tend to promote research, management, and policy that focus only on targeted aspects of the "wicked" wildfire problem. In this article, we provide guiding principles to bridge diverse fire science efforts to advance an integrated agenda of wildfire research that can help overcome disciplinary silos and provide insight on how to build fire-resilient communities.

Understanding the contributions of environmental variation and density feedbacks to changes in vector populations is essential for designing effective vector control. We analyzed monitoring datasets describing larval densities over 7 yr of the two dominant mosquito species, Aedes vigilax (Skuse) and Culex annulirostris (Skuse), of the greater Darwin area (Northern Territory, Australia). Using generalized linear and linear mixed-effects models, we tested hypotheses regarding the environmental determinants of spatio-temporal patterns in relative larval abundance in both species. The most important spatial drivers of Ae. vigilax and Cx. annulirostris larval densities were elevation and water presence. Ae. vigilax density correlates negatively with elevation, whereas there was a positive relationship between Cx. annulirostris density and elevation. These results show how larval habitats used by the saltwater-influenced breeder Ae. vigilax and the obligate freshwater breeder Cx. annulirostris are separated in a tidally influenced swamp. The models examining temporal drivers of larval density also identified this discrimination between freshwater and saltwater habitats. Ae. vigilax larval densities were positively related to maximum tide height and high tide frequency, whereas Cx. annulirostris larval densities were positively related to elevation and rainfall. Adult abundance in the previous month was the most important temporal driver of larval densities in both species, providing a clear dynamical link between the two main life phases in mosquito development. This study shows the importance of considering both spatial and temporal drivers, and intrinsic population dynamics, when planning vector control strategies to reduce larval density, adult population density, and disease transmission effectively.

Background: In 1982, the National Surgical Adjuvant Breast and Bowel Project initiated a randomized, double-blinded, placebo-controlled trial (B-14) to determine the effectiveness of adjuvant tamoxifen therapy in patients with primary operable breast cancer who had estrogen receptor-positive tumors and no axillary lymph node involvement. The findings indicated that tamoxifen therapy provided substantial benefit to patients with early stage disease. However, questions arose about how long the observed benefit would persist, about the duration of therapy necessary to maintain maximum benefit, and about the nature and severity of adverse effects from prolonged treatment., Purpose: We evaluated the outcome of patients in the B-14 trial through 10 years of follow-up. In addition, the effects of 5 years versus more than 5 years of tamoxifen therapy were compared., Methods: In the trial, patients were initially assigned to receive either tamoxifen at 20 mg/day (n = 1404) or placebo (n = 1414). Tamoxifen-treated patients who remained disease free after 5 years of therapy were then reassigned to receive either another 5 years of tamoxifen (n = 322) or 5 years of placebo (n = 321). After the study began, another group of patients who met the same protocol eligibility requirements as the randomly assigned patients were registered to receive tamoxifen (n = 1211). Registered patients who were disease free after 5 years of treatment were also randomly assigned to another 5 years of tamoxifen (n = 261) or to 5 years of placebo (n = 249). To compare 5 years with more than 5 years of tamoxifen therapy, data relating to all patients reassigned to an additional 5 years of the drug were combined. Patients who were not reassigned to either tamoxifen or placebo continued to be followed in the study. Survival, disease-free survival, and distant disease-free survival (relating to failure at distant sites) were estimated by use of the Kaplan-Meier method; differences between the treatment groups were assessed by use of the logrank test. The relative risks of failure (with 95% confidence intervals [CIs]) were determined by use of the Cox proportional hazards model. Reported P values are two-sided., Results: Through 10 years of follow-up, a significant advantage in disease-free survival (69% versus 57%, P < .0001; relative risk = 0.66; 95% CI = 0.58-0.74), distant disease-free survival (76% versus 67%, P < .0001; relative risk = 0.70; 95% CI = 0.61-0.81), and survival (80% versus 76%, P = .02; relative risk = 0.84; 95% CI = 0.71-0.99) was found for patients in the group first assigned to receive tamoxifen. The survival benefit extended to those 49 years of age or younger and to those 50 years of age or older. Tamoxifen therapy was associated with a 37% reduction in the incidence of contralateral (opposite) breast cancer (P = .007). Through 4 years after the reassignment of tamoxifen-treated patients to either continued-therapy or placebo groups, advantages in disease-free survival (92% versus 86%, P = .003) and distant disease-free survival (96% versus 90%, P = .01) were found for those who discontinued tamoxifen treatment. Survival was 96% for those who discontinued tamoxifen compared with 94% for those who continued tamoxifen treatment (P = .08). A higher incidence of thromboembolic events was seen in tamoxifen-treated patients (through 5 years, 1.7% versus 0.4%). Except for endometrial cancer, the incidence of second cancers was not increased with tamoxifen therapy., Conclusions and Implications: The benefit from 5 years of tamoxifen therapy persists through 10 years of follow-up. No additional advantage is obtained from continuing tamoxifen therapy for more than 5 years.

IgD kappa plasma cell Dyscrasias are rare. Two cases with unusual presentations and courses area described. One of these patients had myelomatous pleural effusions, and subsequently experienced myelomatous leptomeningitis. The significance of this combination is discussed and the literature reviewed. The value of immunofluorescent techniques in identifying plasma cells in the cerebrospinal fluid and pleural fluid is emphasized.