Georgetown College

A series of N-aryl sulfonamides was designed, synthesized, and evaluated for their ability to inhibit the bacterial enzyme N-succinyl-L,L-diaminopimelic acid desuccinylase (DapE, EC 3.5.1.18). Our initial lead compound, N-(o-methoxyphenyl)-toluenesulfonamide (4a), identified through a high-throughput screen, showed modest inhibition, with an IC₅₀ of 72.9 μM. Through lead optimization, we improved the potency by modifying key functional groups. Replacing the o-OCH₃ on the aniline ring and p-CH₃ on the sulfonamide ring with p-CF₃ and p-OCH₃, respectively, while retaining the N-CHF₂ hydrophobic moiety, led to our most potent inhibitor, compound 4g (IC₅₀ = 8.9 ± 5.0 μM, Ki = 1.36 ± 0.61 μM), representing an 8-fold increase in potency over hit 4a, and providing the most potent DapE inhibitor yet reported based on the Ki. Molecular docking studies provided insights into this enhanced activity, revealing key interactions within the DapE active site.

High-impact tutoring (HIT) is academic instruction provided in a one-to-one or small group setting by a trained tutor that takes place at least three or more times per week. HIT instruction focuses on cultivating positive student–tutor relationships and supporting students’ knowledge and skill development. HIT has consistently shown large, positive effects on student learning in both math and reading. However, HIT is not easy to implement and program design is often sacrificed. This study aims to understand strategies that school districts have used to maintain fidelity to HIT design while expanding the number of students served. Specifically, districts have often faced challenges hiring enough tutors, providing quality tutor training and curricular resources, ensuring student attendance in tutoring sessions, and utilizing data. In response to staffing challenges, districts have developed multiple options for tutor hiring including recruiting community members, university students, existing school staff, and virtual providers. To support both instructional quality and tutor retention, districts have provided tutor training aligned with tutors’ existing skills and needs, which differs by tutor type. Districts have also improved student attendance by integrating HIT within existing school schedules and clarifying the relationship between HIT and other student support programs.

Patents take the form of public letters that the U.S. Patent and Trademark Office (USPTO) actively disseminates. Whether these documents sufficiently provide the public with notice of the technologies they describe, as well as the proprietary rights that they assert, has been subject to long-standing debate. Many commentators conclude that patents are often filed too early in the research and development cycle, are deliberately drafted in a vague or obtuse manner, or are simply too numerous. As a result, identifying the relevant patent landscape is not just difficult for technology implementers, but possibly undesirable as a matter of innovation policy. Yet prior scholarship has seldom acknowledged current statutory mechanisms to improve the notice function of patents after they issue. This Article endeavors to fill that gap. Congress has long encouraged intellectual property rights holders to identify their patents on the products they sell. Patent marking has traditionally occurred on physical products or their packaging, although it has been recently extended to Internet-based virtual marking. The marking statute stipulates that patent proprietors that fail to mark face severe remedial restrictions when challenging infringers. Congress has assigned the Food & Drug Administration (FDA) a part in providing patent notice as well. In keeping with federal legislation, the agency maintains two publications, commonly known as the Orange and Purple Books, that act as a patent clearinghouse for approved drugs and licensed biologics. The role of a patent within the marketplace provides perhaps the most valuable form of notice that that instrument may offer. Yet the marking statute and FDA publications suffer from some apparent flaws. In combination they project a failure to identify all patents that are relevant to the product, favor patent trolls, involve dubious practical workings, promote misleading advertising, and impose punitive sanctions in comparison to the notice requirements of peer intellectual property rights. For its part, the FDA has proven an untutored and unreliable patent publicist for the past four decades. This Article offers specific suggestions to improve the notice functions of patents after they issue. It calls for the USPTO to develop and populate its own virtual marking database that correlates individual patents with the marketplace. It also encourages the FDA to take further steps to counter abuses of the Orange and Purple Books and to accelerate their patent notice functions. Finally, this Article takes broader lessons from this effort, offering pathways for policymakers to look beyond the patent instrument as they endeavor to improve the patent system’s notice functions.

e19055 Background: Peripheral and cutaneous T-cell lymphomas (PTCL and CTCL) comprise of a vast variety of rare and heterogeneous subtypes of non-Hodgkin lymphomas, accounting for almost 15-20% of all lymphomas, with poor prognoses and limited treatment options. The study aims to explore 20-year mortality trends which might help in identifying vulnerable populations and addressing inequities ultimately leading to better survival rates. Methods: We conducted an examination of death certificates sourced from the CDC WONDER database (Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research) from 1999 to 2020. Mortality rate due to peripheral and cutaneous T-cell lymphomas was assessed using the ICD code C84. Age-Adjusted Mortality Rates (AAMRs) per 100,000 persons, Average Annual Percentage Change (AAPC) and Annual Percent Change (APC) were reported. APCs in AAMRs with 95% CI were obtained using joint point regression analysis across different demographic and geographic subgroups. Results: The AAMR for Peripheral and Cutaneous T-cell lymphomas increased from 0.234 (upper CI=95%; 0.216 to 0.253) in 1999 to 0.343 (upper CI=95%; 0.324 to 0.362) in 2020 with an APC of 4.76% from 1999-2006, followed by an increase of 1.09% from 2006-2020 (p<0.000001). Females exhibited higher AAMRs than males (p= 0.04). Large central metropolitan areas had an increased AAPC (2.647) followed by non-metropolitan areas (AAPC=1.504). The 75-84 year age group reported the highest mortality with 5967 deaths (AAPC=3.747) whereas lower death rates were reported by younger age groups. The North-east reported the highest AAMR (0.392; 95% upper CI, 0.344 to 0.44) followed by South (0.313; upper CI=95%, 0.306 to 0.32), West (0.313; upper CI=95%, 0.304 to 0.322) and mid-West (0.312; upper CI=95%, 0.303 to 0.321). The Black or African American reported the highest AAMR and an APC of 1.908%, p= 0.000032. Pennsylvania had the highest APC (2.881%) whereas a decrease in mortality was observed in California after 2010 (APC=-1.410%,p=0.000013). Conclusions: Over the last two decades, there has been an overall increase in the mortality rate due to peripheral and cutaneous T-cell lymphomas in the United States. Increased AAMRs have been reported by females, older age groups, metropolitan areas, Black or African Americans, North-west regions and states like Pennsylvania representing various disparities among the trends. Interestingly, California reported a decreased mortality during the last decade. These variations in the trends necessitate the need for additional exploration and targeted interventions.

This case uses the COVID-19 crisis experience to consider the complex dimensions of crisis and the impact of that complexity on crisis leadership. The case challenges students to consider how this, and other, crises are catalytic events that unleash social, political, and economic forces for which school and district leaders must prepare.