On the Complexity and Performance of Parsing with Derivatives

Current algorithms for context-free parsing inflict a trade-off between ease of understanding, ease of implementation, theoretical complexity, and practical performance. No algorithm achieves all of these properties simultaneously. Might et al. (2011) introduced parsing with derivatives, which handles arbitrary context-free grammars while being both easy to understand and simple to implement. Despite much initial enthusiasm and a multitude of independent implementations, its worst-case complexity has never been proven to be better than exponential. In fact, high-level arguments claiming it is fundamentally exponential have been advanced and even accepted as part of the folklore. Performance ended up being sluggish in practice, and this sluggishness was taken as informal evidence of exponentiality. In this paper, we reexamine the performance of parsing with derivatives. We have discovered that it is not exponential but, in fact, cubic. Moreover, simple (though perhaps not obvious) modifications to the implementation by Might et al. (2011) lead to an implementation that is not only easy to understand but also highly performant in practice.Comment: 13 pages; 12 figures; implementation at http://bitbucket.org/ucombinator/parsing-with-derivatives/ ; published in PLDI '16, Proceedings of the 37th ACM SIGPLAN Conference on Programming Language Design and Implementation, June 13 - 17, 2016, Santa Barbara, CA, US

Adaptively Biased Molecular Dynamics for Free Energy Calculations

We present an Adaptively Biased Molecular Dynamics (ABMD) method for the computation of the free energy surface of a reaction coordinate using non-equilibrium dynamics. The ABMD method belongs to the general category of umbrella sampling methods with an evolving biasing potential, and is inspired by the metadynamics method. The ABMD method has several useful features, including a small number of control parameters, and an $O(t)$ numerical cost with molecular dynamics time $t$. The ABMD method naturally allows for extensions based on multiple walkers and replica exchange, where different replicas can have different temperatures and/or collective variables. This is beneficial not only in terms of the speed and accuracy of a calculation, but also in terms of the amount of useful information that may be obtained from a given simulation. The workings of the ABMD method are illustrated via a study of the folding of the Ace-GGPGGG-Nme peptide in a gaseous and solvated environment.Comment: Revised version to appear in Journal of Chemical Physic

Nature, Feminism, and Flourishing: Human Nature and the Feminist Ethics of Flourishing

This dissertation examines the viability of a feminist ethic of flourishing. The possibility of a eudaimonist, or flourishing-based, ethic adapted for the needs of feminist ethics and politics has recently been raised by a number of feminist moral philosophers. However, in these discussions, the degree to which an ethic of flourishing requires a substantive conception of human nature has not been adequately addressed. Flourishing-based ethical theories appear to require a substantive account of the kind of thing whose flourishing is to be promoted, while contemporary academic feminism is characterized by a strong suspicion toward claims about human nature. Chapter one situates this problem in the current literature and reframes feminist anti-essentialist objections to nature claims. Chapter two analyzes three historically influential exemplars of the ethics of flourishing: Aristotle, Hume, and Marx. Employing the analytic categories developed in chapter two, chapters three through five assess the work of Rosalind Hursthouse, Martha Nussbaum, and Lisa Tessman for their adequacy to serve as the basis of a feminist ethic of flourishing. I argue that each has something of value to offer and yet each is problematic when it comes to how they appeal (or fail to appeal) to human nature. The central argument of this dissertation is that, properly understood, a theory of human nature can be a critical resource for a feminist ethic of flourishing. As such, feminist moral philosophers who would condemn oppression, gender-based subordination, and other injustices by appealing to an ideal of flourishing that is being denied or cut off, would benefit from greater attention to the assumptions about human nature that such theories of flourishing entail. On the view defended here, a normative conception of human nature is a necessary methodological element of a flourishing-based ethical theory that illuminates the reasons one has in support of a particular vision of flourishing. While I leave open the question of how such a conception of human nature could be objectively justified, this dissertation argues that a theory of human nature can serve as a normative resource for feminist moral criticism within a flourishing-based ethical framework

Nature, Feminism, and Flourishing: Human Nature and the Feminist Ethics of Flourishing

This dissertation examines the viability of a feminist ethic of flourishing. The possibility of a eudaimonist, or flourishing-based, ethic adapted for the needs of feminist ethics and politics has recently been raised by a number of feminist moral philosophers. However, in these discussions, the degree to which an ethic of flourishing requires a substantive conception of human nature has not been adequately addressed. Flourishing-based ethical theories appear to require a substantive account of the kind of thing whose flourishing is to be promoted, while contemporary academic feminism is characterized by a strong suspicion toward claims about human nature. Chapter one situates this problem in the current literature and reframes feminist anti-essentialist objections to nature claims. Chapter two analyzes three historically influential exemplars of the ethics of flourishing: Aristotle, Hume, and Marx. Employing the analytic categories developed in chapter two, chapters three through five assess the work of Rosalind Hursthouse, Martha Nussbaum, and Lisa Tessman for their adequacy to serve as the basis of a feminist ethic of flourishing. I argue that each has something of value to offer and yet each is problematic when it comes to how they appeal (or fail to appeal) to human nature. The central argument of this dissertation is that, properly understood, a theory of human nature can be a critical resource for a feminist ethic of flourishing. As such, feminist moral philosophers who would condemn oppression, gender-based subordination, and other injustices by appealing to an ideal of flourishing that is being denied or cut off, would benefit from greater attention to the assumptions about human nature that such theories of flourishing entail. On the view defended here, a normative conception of human nature is a necessary methodological element of a flourishing-based ethical theory that illuminates the reasons one has in support of a particular vision of flourishing. While I leave open the question of how such a conception of human nature could be objectively justified, this dissertation argues that a theory of human nature can serve as a normative resource for feminist moral criticism within a flourishing-based ethical framework

Using Interviews to Understand Patients’ Post-operative Pain Management Educational Needs Before and After Elective Total Joint Replacement Surgery

Objective: To better understand the education needs of patients electing to have TJR in managing their pain in the post-operative period after discharge from the hospital. Methods: An exploratory, descriptive, qualitative design. Convenience sample of people who reported that they had not received information about pain management prior to TJR surgery were recruited from 9 surgeon practices in 8 states to participate in telephone interviews, utilizing open-ended questions. Questions included: recollection of pre-op class attended and content; experiences with surgical pain after surgery and how it was managed; experiences with pain medicine; experience using non-medicine related pain reduction methods; suggestions for delivery of pain management information. Interviews were recorded and transcribed. Data were categorized using content analysis techniques. Results: Seventeen patients were interviewed. Although all remembered attending a pre-operative class prior to their joint replacement surgery, none remembered receiving information during that class about managing pain once they were discharged. All had been prescribed an opioid for pain management post-operatively; however no patients reported receiving any information regarding use of the medication other than the information on the pill bottle. Many had concerns regarding the use of opioids to control their pain, including side effects, such as constipation and the risk of addiction. The most common non-medicine method used to manage pain was the use of ice. Participants believed that information about pain management, including both non-medicine approaches and instructions for taking opioids would be helpful and should be delivered at multiple time points, including pre-operatively, at discharge, and within the first few days after discharge. Conclusion: With trends toward shorter hospital stays, home based pain management is a priority. Understanding the pain management education needs of patients considering elective TJR could inform interventions for this population as well as provide insight into the needs of other patients undergoing surgery

Confidential genetic testing and electronic health records: A survey of current practices among Huntington disease testing centers

BACKGROUND: Clinical care teams providing presymptomatic genetic testing often employ advanced confidentiality practices for documentation and result storage. However, patient requests for increased confidentiality may be in conflict with the legal obligations of medical providers to document patient care activities in the electronic health record (EHR). Huntington disease presents a representative case study for investigating the ways centers currently balance the requirements of EHRs with the privacy demands of patients seeking presymptomatic genetic testing. METHODS: We surveyed 23 HD centers (53% response rate) regarding their use of the EHR for presymptomatic HD testing. RESULTS: Our survey revealed that clinical care teams and laboratories have each developed their own practices, which are cumbersome and often include EHR avoidance. We found that a majority of HD care teams record appointments in the EHR (91%), often using vague notes. Approximately half of the care teams (52%) keep presymptomatic results of out of the EHR. CONCLUSION: As genetic knowledge grows, linking more genes to late-onset conditions, institutions will benefit from having professional recommendations to guide development of policies for EHR documentation of presymptomatic genetic results. Policies must be sensitive to the ethical differences and patient demands for presymptomatic genetic testing compared to those undergoing confirmatory genetic testing

Ancestry-Dependent Enrichment of Deleterious Homozygotes in Runs of Homozygosity.

Runs of homozygosity (ROH) are important genomic features that manifest when an individual inherits two haplotypes that are identical by descent. Their length distributions are informative about population history, and their genomic locations are useful for mapping recessive loci contributing to both Mendelian and complex disease risk. We have previously shown that ROH, and especially long ROH that are likely the result of recent parental relatedness, are enriched for homozygous deleterious coding variation in a worldwide sample of outbred individuals. However, the distribution of ROH in admixed populations and their relationship to deleterious homozygous genotypes is understudied. Here we analyze whole-genome sequencing data from 1,441 unrelated individuals from self-identified African American, Puerto Rican, and Mexican American populations. These populations are three-way admixed between European, African, and Native American ancestries and provide an opportunity to study the distribution of deleterious alleles partitioned by local ancestry and ROH. We re-capitulate previous findings that long ROH are enriched for deleterious variation genome-wide. We then partition by local ancestry and show that deleterious homozygotes arise at a higher rate when ROH overlap African ancestry segments than when they overlap European or Native American ancestry segments of the genome. These results suggest that, while ROH on any haplotype background are associated with an inflation of deleterious homozygous variation, African haplotype backgrounds may play a particularly important role in the genetic architecture of complex diseases for admixed individuals, highlighting the need for further study of these populations

Response of human engineered cartilage based on articular or nasal chondrocytes to interleukin-1? and low oxygen

Previous studies showed that human nasal chondrocytes (HNC) exhibit higher proliferation and chondrogenic capacity as compared to human articular chondrocytes (HAC). To consider HNC as a relevant alternative cell source for the repair of articular cartilage defects it is necessary to test how these cells react when exposed to environmental factors typical of an injured joint. We thus aimed this study at investigating the responses of HNC and HAC to exposure to interleukin (IL)-1? and low oxygen. For this purpose HAC and HNC harvested from the same donors (N=5) were expanded in vitro and then cultured in pellets or collagen-based scaffolds at standard (19%) or low oxygen (5%) conditions. Resulting tissues were analyzed after a short (3 days) exposure to IL-1?, mimicking the initially inflammatory implantation site, or following a recovery time (1 or 2 weeks for pellets and scaffolds, respectively). After IL-1? treatment, constructs generated by both HAC and HNC displayed a transient loss of GAG (up to 21.8% and 36.8%, respectively) and, consistently, an increased production of metalloproteases (MMP)-1 and -13. Collagen type II and the cryptic fragment of aggrecan (DIPEN), both evaluated immunohistochemically, displayed a trend consistent with GAG and MMPs production. HNC-based constructs exhibited a more efficient recovery upon IL-1? withdrawal, resulting in a higher accumulation of GAG (up to 2.6-fold) compared to the corresponding HAC-based tissues. On the other hand, HAC displayed a positive response to low oxygen culture, while HNC were only slightly affected by oxygen percentage. Collectively, under the conditions tested mimicking the postsurgery articular environment, HNC retained a tissue-forming capacity, similar or even better than HAC. These results represent a step forward in validating HNC as a cell source for cartilage tissue engineering strategies

Effective Pain Information Pre-operatively is Associated with Improved Functional Gain after Total Joint Replacement

Objective: We evaluated receipt of pre-operative pain management education in a national prospective cohort on post-operative pain and function. Methods: Preoperative, 2 week and 6 month postoperative data from a nationally representative cohort of 1404 primary unilateral TJR patients with a date of surgery between May 2011 and December 2014. Data included demographics, comorbid conditions, operative joint pain severity (HOOS/KOOS), musculoskeletal disease burden, physical function (SF36 PCS), and mental health (SF36 MCS). At 2 weeks post-op, patients were asked if they had received information prior to surgery about pain management options and if so, how helpful the information was. Additionally, patients were asked about use of non-medication methods to relieve operative joint pain. Descriptive statistics were performed. Results: One third reported not receiving information about pain management; an additional 11% did not find it helpful. There were no differences pre-operatively in demographics, comorbid conditions, operative joint pain severity, musculoskeletal disease burden, SF36 PCS and MCS between those who received information and those who did not. Patients who received information about pain management options were more likely to use non-medication methods to relieve operative joint pain (p\u3c 0.000). They reported less current pain (p = 0.02) and maximum pain (p = 0.03) in their operative joint at 2 weeks post-op. At 6 months post-op, patients who reported not receiving information about pain management had statistically lower physical function scores that those receiving information (p = 0.04). There was no difference in HOOS/KOOS pain scores 6 months post-op. Conclusion: More than 40% of TJR patients in this study reported that they did not receive or received unhelpful information regarding post-op pain management options, highlighting a need for more consistent patient education. In this study, the lack of pain management information appears to negatively impact 6 month post-operative function