The Effect of the Uniform Bar Examination on Admissions, Diversity, Affordability, and Employment across Law Schools in the United States

The Uniform Bar Examination (UBE), first implemented in February 2011 in Missouri and North Dakota, is a multijurisdictional or cross-state test designed to assess a minimum shared core of legal knowledge and lawyering skills. Since its implementation, UBE has now reached 37 states and territories, including the District of Columbia. Despite this prevalence, no empirical evidence exists regarding its effects on law schools’ admissions, diversity, affordability, and employment mobility of law students and graduates or of its effects on law schools’ application volumes or average bar passage rates. This study addresses this gap by providing a comprehensive examination of the effects of UBE adoption. Specifically, we apply rigorous quasi-experimental and causal-inference methods to a law-school level dataset to test whether UBE adoption influenced admissions, enrollment, affordability, degree production, bar passage rates, and employment mobility for law schools in UBE states. Our findings indicate that institutions located in states participating in UBE (compared to institutions located in states where no UBE has been implemented) realized higher applications (nearly 9% increase) and higher enrollments (reaching increases over 6% in total JD enrollments). We also found that these increases were driven predominantly by White student enrollments and women enrollees. With respect to affordability, no changes were observed in neither tuition increases and net price changes. Despite increase in enrollment, we found no evidence of increases in neither degree production nor in Bar passing rates. Based on this findings, we can conclude that UBE has had an effect in applications and enrollment, but if UBE aims to affect the diversification of the law profession, this program alone may be falling short in expanding access for minoritized students

Unleashing the full potential of Hsp90 inhibitors as cancer therapeutics through simultaneous inactivation of Hsp90, Grp94, and TRAP1

Cancer therapeutics: Extending a drug's reach A new drug that blocks heat shock proteins (HSPs), helper proteins that are co-opted by cancer cells to promote tumor growth, shows promise for cancer treatment. Several drugs have targeted HSPs, since cancer cells are known to hijack these helper proteins to shield themselves from destruction by the body. However, the drugs have had limited success. Hye-Kyung Park and Byoung Heon Kang at Ulsan National Institutes of Science and Technology in South Korea and coworkers noticed that the drugs were not absorbed into mitochondria, a key cellular compartment, and HSPs in this compartment were therefore not being blocked. They identified a new HSP inhibitor that can reach every cellular compartment and inhibit all HSPs. Testing in mice showed that this inhibitor effectively triggered death of tumor cells, and therefore shows promise for anti-cancer therapy. The Hsp90 family proteins Hsp90, Grp94, and TRAP1 are present in the cell cytoplasm, endoplasmic reticulum, and mitochondria, respectively; all play important roles in tumorigenesis by regulating protein homeostasis in response to stress. Thus, simultaneous inhibition of all Hsp90 paralogs is a reasonable strategy for cancer therapy. However, since the existing pan-Hsp90 inhibitor does not accumulate in mitochondria, the potential anticancer activity of pan-Hsp90 inhibition has not yet been fully examined in vivo. Analysis of The Cancer Genome Atlas database revealed that all Hsp90 paralogs were upregulated in prostate cancer. Inactivation of all Hsp90 paralogs induced mitochondrial dysfunction, increased cytosolic calcium, and activated calcineurin. Active calcineurin blocked prosurvival heat shock responses upon Hsp90 inhibition by preventing nuclear translocation of HSF1. The purine scaffold derivative DN401 inhibited all Hsp90 paralogs simultaneously and showed stronger anticancer activity than other Hsp90 inhibitors. Pan-Hsp90 inhibition increased cytotoxicity and suppressed mechanisms that protect cancer cells, suggesting that it is a feasible strategy for the development of potent anticancer drugs. The mitochondria-permeable drug DN401 is a newly identified in vivo pan-Hsp90 inhibitor with potent anticancer activity

Endocardial Fibroelastosis in a 57-Year-Old Transplant Recipient

Endocardial fibroelastosis (EFE) is characterized by deposition of collagen and elastin leading to ventricular hypertrophy and diffuse endocardial thickening. Here we report (for the first time in Korea) the case of a EFE presenting with heart failure. The patient was a 57-year-old woman who had complained of dyspnea on exertion {New York Heart Association (NYHA) functional class 3} and abdominal distension at the time of hospital admission. Echocardiography showed severe diastolic dysfunction with normal systolic function. On MRI, the contrast-enhanced delayed myocardial image demonstrated hyperenhancement in the endocardium. Owing to progressive heart failure, the patient was transplanted. Histological examination of the explanted heart showed irregularly thickened endocardium with fibrosis and elastosis in the both ventricles, compatible with the diagnosis of EFE

Polymorphisms in Genes That Regulate Cyclosporine Metabolism Affect Cyclosporine Blood Levels and Clinical Outcomes in Patients Who Receive Allogeneic Hematopoietic Stem Cell Transplantation

In patients who received allogeneic hematopoietic stem cell transplantation (HSCT), we investigated the correlations between single nucleotide polymorphisms (SNPs) in genes that regulate cyclosporine metabolism and clinical outcomes. All patients received sibling-matched HSCT. DNA samples of patients and donors were analyzed for 4 SNPs: MDR1 +1236C>T (rs1128503), +2677G>T>A (rs2032582), +3435C>T (rs1045642), and CYP3A5 +6986G>A (rs776746). A total of 156 patients (median age 40 years) were analyzed. Nineteen patients received HSCT for nonmalignant disease. The CYP3A5 +6986AA genotype was associated with a high cyclosporine blood level after transplantation. However, this genotype was not related to any particular clinical outcome. In contrast, the MDR1 +1236C>T SNP was correlated with specific clinical outcomes. When neither the donor nor the recipient had the CC genotype of MDR1 +1236, patients had lower creatinine levels (P < .001) and less transplantation-related mortality (TRM) (P = .012). These patients also showed longer overall survival (OS) in both univariate (P = .003) and multivariate (P = .003) analyses. Although the CYP3A5 +6986AA genotype was correlated with a high blood cyclosporine concentration, lack of the MDR1 +1236CC genotype in both the donor and recipient was correlated with less TRM and a longer OS in patients who received allogeneic HSCT

Production of transgenic first filial puppies expressing mutated human amyloid precursor protein gene

Propagation of transgenic animals by germline transmission using assisted reproductive technologies such as in vitro fertilization (IVF) is the most efficient way to produce transgenic colonies for biomedical research. The objective of this study was to generate transgenic puppies from a founder dog expressing the mutated human amyloid precursor protein (mhAPP) gene. Experiment I assessed the characteristics of the semen prepared by freshly diluted, swim-up, and Percoll gradient methods using a computer-assisted semen analyzer (CASA). Motile and progressively motile sperm counts were higher in the Percoll gradient samples (p &lt; 0.05) than in the swim-up and freshly diluted samples. In Experiment II, a total of 59, 70, and 65 presumptive zygotes produced by fresh, Percoll gradient, and swim-up methods, respectively, were transferred to surrogates (5 for each group); the Percoll gradient (27.27%) and swim-up samples (14.29%) showed the highest blastocyst formation rates, while fresh diluted semen did not produce any blastocyst. Experiment III examined the full-term developmental ability of embryos. Among the 5 surrogates in the Percoll gradient group, one (20.0%) became pregnant; it had 4 (6.15%) sacs and delivered 4 (6.15%; 2 males and 2 females) live puppies. Among the 4 puppies, 2 (50.0%) were found to transmit the transgene on their nail and toe under GFP fluorescence. Furthermore, the integration and expression of the mhAPP transgene were examined in the umbilical cords of all the IVF-derived puppies, and the presence of the transgene was only observed in the GFP-positive puppies. Thus, semen prepared by the Percoll method could generate transgenic puppies by male germline transmission using the IVF technique. Our result will help propagate transgenic dogs efficiently, which will foster human biomedical research

A Case of Acute Myocardial Infarction Caused by Distal Embolization of a Left Main Coronary Artery Thrombus

Coronary embolism is an uncommon cause of myocardial infarction. A 48-year-old male presented with typical chest pain of an MI. There was no definite ST segment change on electrocardiogram (ECG) and no elevation of myocardial enzymes. Coronary angiography (CAG) revealed occlusion of the distal left anterior descending coronary artery (dLAD), the distal left circumflex coronary artery (dLCX), the diagonal branch (D) and the obtuse marginal branch (OM), with a large filling defect in the left main coronary artery (LMA) that caused the myocardial infarction. We considered the possibility that coronary embolization was caused by the migration of a thrombus in the LMA during CAG. We did balloon angioplasty in the dLAD, dLCX, OM and D and treated the patient with glycoprotein IIb/IIIa receptor antagonist. However, thrombi remained in the dLAD, OM, and dLCX. After 3 days of anti-thrombotic treatment, follow-up CAG revealed only slight resolution of thrombi in the LAD. After triple antiplatelet agent medication for 1 year, a follow-up CAG showed a resolution of the thrombi in all coronary arteries