The Aspiring Attorney with ADHD: Bar Accommodations or a Bar to Practice?

This Article is the first in the academic literature to examine how a strict application of the childhood history requirement reduces the likelihood that applicants will receive ADHD accommodations on the bar exam based on race, sex, socioeconomic status, location, and age. Part One provides an introduction to ADHD, explaining the diagnostic framework and its limitations, specifically with regard to childhood diagnosis and adult ADHD. Part Two describes the legal and policy framework applicable to bar examiner agencies, focusing on the Americans with Disabilities Act ( ADA ). The Article sets forth, in Part Three, state bar policies and practices regarding ADHD accommodations. Within that context, Part Four demonstrates how the childhood history requirement exposes state bars to liability under the ADA. Part Five reveals how the childhood history requirement negatively impacts protected classes and, thus, the diversity of the legal profession. Finally, the analysis concludes in Part Six with specific, groundbreaking recommendations to address and mitigate the injustice that bar applicants from underrepresented populations in the profession

Balancing innovation and access: India’s pharmaceutical patent laws

Writing in Science, LSE’s Kenneth Shadlen, Bhaven Sampat (Columbia) and Tahir Amin (Harvard) debate the implications of an upcoming Indian Supreme Court decision on pharmaceutical patents for variants of existing compounds and its impact on the accessibility of affordable drugs

Increased prevalence of val(66)met BDNF genotype among subjects with cervical dystonia

Abnormalities of cortical representational maps and their plasticity have been described in dystonia. A common polymorphism for BDNF has been associated with abnormal cortical plasticity, and thus might contribute to pathogenesis of dystonia in some subjects. As a first step towards this suggestion, the current study examined the prevalence of this polymorphism. BDNF genotype was examined in 34 subjects with cervical dystonia, 54 age-matched healthy controls, and 53 subjects with a different movement disorder, Parkinson\u27s disease. ApoE genotype, known to influence neurological outcome in some conditions, was also examined as a control. In subjects with cervical dystonia, the val(66)met polymorphism was approximately twice as prevalent when compared to either control group. This was not true of ApoE genotype, which was similarly distributed across subject groups. The current findings suggest that the BDNF val(66)met polymorphism might play a role in the pathogenesis of cervical dystonia in some subjects

Correcting Model Misspecification via Generative Adversarial Networks

Machine learning models are often misspecified in the likelihood, which leads to a lack of robustness in the predictions. In this paper, we introduce a framework for correcting likelihood misspecifications in several paradigm agnostic noisy prior models and test the model's ability to remove the misspecification. The "ABC-GAN" framework introduced is a novel generative modeling paradigm, which combines Generative Adversarial Networks (GANs) and Approximate Bayesian Computation (ABC). This new paradigm assists the existing GANs by incorporating any subjective knowledge available about the modeling process via ABC, as a regularizer, resulting in a partially interpretable model that operates well under low data regimes. At the same time, unlike any Bayesian analysis, the explicit knowledge need not be perfect, since the generator in the GAN can be made arbitrarily complex. ABC-GAN eliminates the need for summary statistics and distance metrics as the discriminator implicitly learns them and enables simultaneous specification of multiple generative models. The model misspecification is simulated in our experiments by introducing noise of various biases and variances. The correction term is learnt via the ABC-GAN, with skip connections, referred to as skipGAN. The strength of the skip connection indicates the amount of correction needed or how misspecified the prior model is. Based on a simple experimental setup, we show that the ABC-GAN models not only correct the misspecification of the prior, but also perform as well as or better than the respective priors under noisier conditions. In this proposal, we show that ABC-GANs get the best of both worlds

TRIPS implementation and secondary pharmaceutical patenting in Brazil and India

This article compares national approaches toward secondary pharmaceutical patents. Because secondary patents can extend periods of exclusivity and delay generic competition, they can raise prices and reduce access to medicines. Little is known about what measures countries have enacted policies to address applications for secondary pharmaceutical patents, how they function, and whether, in practice, these measures limit secondary patents. We analyze the cases of India and Brazil. We assemble data on pharmaceutical patent applications filed in the two countries, code each application to identify which constitute secondary applications, and examine outcomes for each application in both countries. The data indicate that Brazil is less likely to grant applications than India, but in both countries the measures designed to limit secondary patents are having little direct effect. This suggests, on the one hand, that critics of these policies, such as the transnational pharmaceutical sector and foreign governments, may be more worried than they should be. On the other hand, champions of the policies, such as NGOs and international organizations, may have cause for concern that laws on the books are not having the expected impact on patent outcomes in practice. Our findings also suggest that, at the drug level, the effects of countries’ approaches toward secondary patents need to be understood in the context of their broader approaches toward TRIPS implementation, including when and how they introduced pharmaceutical patents in the 1990s and 2000s

Polyamines Drive Myeloid Cell Survival by Buffering Intracellular pH to Promote Immunosuppression in Glioblastoma

Glioblastoma is characterized by the robust infiltration of immunosuppressive tumor-associated myeloid cells (TAMCs). It is not fully understood how TAMCs survive in the acidic tumor microenvironment to cause immunosuppression in glioblastoma. Metabolic and RNA-seq analysis of TAMCs revealed that the arginine-ornithine-polyamine axis is up-regulated in glioblastoma TAMCs but not in tumor-infiltrating CD8+ T cells. Active de novo synthesis of highly basic polyamines within TAMCs efficiently buffered low intracellular pH to support the survival of these immunosuppressive cells in the harsh acidic environment of solid tumors. Administration of difluoromethylornithine (DFMO), a clinically approved inhibitor of polyamine generation, enhanced animal survival in immunocompetent mice by causing a tumor-specific reduction of polyamines and decreased intracellular pH in TAMCs. DFMO combination with immunotherapy or radiotherapy further enhanced animal survival. These findings indicate that polyamines are used by glioblastoma TAMCs to maintain normal intracellular pH and cell survival and thus promote immunosuppression during tumor evolution

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty