The Association between Preoperative Instruction on Length of Hospital Stay in Total Knee Replacements

Preoperative instruction has been a critical aspect of surgical procedure since the 1970s when hospitals started formal programs. With the recent push for health care reform, all aspects of the medical profession are looking toward cost reduction. This independent study proposal was designed to assess the comparison of length of hospitalization in total knee replacement patients who have preoperative instruction versus those who do not receive preoperative instruction. Problem with the prior research involving preoperative teaching included the following: a wide variety of surgical diagnoses, the number of different physicians performing the surgeries, the small sample sizes, and outdated literature. The proposal employs a chart review of an experimental group-control group design. The experimental group teaching program includes viewing a 10-minute video concerning total knee replacement; question/answer session with nursing staff; and review of total knee replacement exercises, transfers, and ambulation with a physical therapist. Patient charts were randomly chosen from the time period January 1, 1990 through December 31, 1991. Each chart met the criteria for selection. Twenty charts were analyzed from each group to determine the average length of hospitalization. An analysis of variance of means was completed, with appropriate Hest application at the 0.05 level of significance. The implications of this study indicate that additional steps must be taken to continue quality of patient care while reducing overall medical costs. The advent of the preoperative instruction is one quarter of a century old and requires updated data for justification of its use

Conformal Supergravity Tree Amplitudes from Open Twistor String Theory

We display the vertex operators for all states in the conformal supergravity sector of the twistor string, as outlined by Berkovits and Witten. These include `dipole' states, which are pairs of supergravitons that do not diagonalize the translation generators. We use canonical quantization of the open string version of Berkovits, and compute N-point tree level scattering amplitudes for gravitons, gluons and scalars. We reproduce the Berkovits-Witten formula for maximal helicity violating (MHV) amplitudes (which they derived using path integrals), and extend their results to the dipole pairs. We compare these trees with those of Einstein gravity field theory.Comment: 31 pages, expanded version, references adde

Genome-Scale CRISPR Screens Identify Human Pluripotency-Specific Genes

Human pluripotent stem cells (hPSCs) generate a variety of disease-relevant cells that can be used to improve the translation of preclinical research. Despite the potential of hPSCs, their use for genetic screening has been limited by technical challenges. We developed a scalable and renewable Cas9 and sgRNA-hPSC library in which loss-of-function mutations can be induced at will. Our inducible mutant hPSC library can be used for multiple genome-wide CRISPR screens in a variety of hPSC-induced cell types. As proof of concept, we performed three screens for regulators of properties fundamental to hPSCs: their ability to self-renew and/or survive (fitness), their inability to survive as single-cell clones, and their capacity to differentiate. We identified the majority of known genes and pathways involved in these processes, as well as a plethora of genes with unidentified roles. This resource will increase the understanding of human development and genetics. This approach will be a powerful tool to identify disease-modifying genes and pathways

Toward realistic integrable gauge theories and conformal gravity in twistor strings

This dissertation concerns two topics. We first discuss the Yangian structure of deformed integral, four-dimensional N=4 super Yang-Mills theories using Yangians. We use twist deformations in the Yangian coproducts, which are known to maintain the integrable structure. In a five-state subset of states we examine two explicit cases of deformation resulting in SU(2)xU(1)3 and SU(2|1)xU(1)2, which are subgroups of the N=1 residual supersymmetry, PSU(2,2|1), in the full theory. While the full PSU(2,2|4) Yangian structure is manifest in the deformed theory, we show how the symmetry breaking to N=1 is produced via twisted coproducts. For the second topic, we display the vertex operators for all states in the conformal supergravity sector of twistor string theory. Using canonical quantization of the open string, we compute N-point tree amplitudes for the supergraviton states. These include amplitudes involving the dipole gravitons, which are not eigenstates of the translation generator. The conformal gravity amplitudes would be hard to access using conventional field theory methods

Yangians in Deformed Super Yang-Mills Theories

We discuss the integrability structure of deformed, four-dimensional N=4 super Yang-Mills theories using Yangians. We employ a recent procedure by Beisert and Roiban that generalizes the beta deformation of Lunin and Maldacena to produce N=1 superconformal gauge theories, which have the superalgebra SU(2,2|1)xU(1)xU(1). The deformed theories, including those with the more general twist, were shown to have retained their integrable structure. Here we examine the Yangian algebra of these deformed theories. In a five field subsector, we compute the two cases of SU(2)xU(1)xU(1)xU(1) and SU(2|1)xU(1)xU(1) as residual symmetries of SU(2,2|1)xU(1)xU(1). We compute a twisted coproduct for these theories, and show that only for the residual symmetry do we retain the standard coproduct. The twisted coproduct thus provides a method for symmetry breaking. However, the full Yangian structure of SU(2|3) is manifest in our subsector, albeit with twisted coproducts, and provides for the integrability of the theory.Comment: 17 page

Quantum Symmetries and Marginal Deformations

We study the symmetries of the N=1 exactly marginal deformations of N=4 Super Yang-Mills theory. For generic values of the parameters, these deformations are known to break the SU(3) part of the R-symmetry group down to a discrete subgroup. However, a closer look from the perspective of quantum groups reveals that the Lagrangian is in fact invariant under a certain Hopf algebra which is a non-standard quantum deformation of the algebra of functions on SU(3). Our discussion is motivated by the desire to better understand why these theories have significant differences from N=4 SYM regarding the planar integrability (or rather lack thereof) of the spin chains encoding their spectrum. However, our construction works at the level of the classical Lagrangian, without relying on the language of spin chains. Our approach might eventually provide a better understanding of the finiteness properties of these theories as well as help in the construction of their AdS/CFT duals.Comment: 1+40 pages. v2: minor clarifications and references added. v3: Added an appendix, fixed minor typo

Structure of the string R-matrix

By requiring invariance directly under the Yangian symmetry, we rederive Beisert's quantum R-matrix, in a form that carries explicit dependence on the representation labels, the braiding factors, and the spectral parameters u_i. In this way, we demonstrate that there exist a rewriting of its entries, such that the dependence on the spectral parameters is purely of difference form. Namely, the latter enter only in the combination u_1-u_2, as indicated by the shift automorphism of the Yangian. When recasted in this fashion, the entries exhibit a cleaner structure, which allows to spot new interesting relations among them. This permits to package them into a practical tensorial expression, where the non-diagonal entries are taken care by explicit combinations of symmetry algebra generators.Comment: 9 pages, LaTeX; typos correcte

Editing the genome of chicken primordial germ cells to introduce alleles and study gene function

With continuing advances in genome sequencing technology, the chicken genome assembly is now better annotated with improved accuracy to the level of single nucleotide polymorphisms. Additionally, the genomes of other birds such as the duck, turkey and zebra finch have now been sequenced. A great opportunity exists in avian biology to use genome editing technology to introduce small and defined sequence changes to create specific haplotypes in chicken to investigate gene regulatory function, and also perform rapid and seamless transfer of specific alleles between chicken breeds. The methods for performing such precise genome editing are well established for mammalian species but are not readily applicable in birds due to evolutionary differences in reproductive biology. A significant leap forward to address this challenge in avian biology was the development of long-term culture methods for chicken primordial germ cells (PGCs). PGCs present a cell line in which to perform targeted genetic manipulations that will be heritable. Chicken PGCs have been successfully targeted to generate genetically modified chickens. However, genome editing to introduce small and defined sequence changes has not been demonstrated in any avian species. To address this deficit, the application of CRISPR/Cas9 and short oligonucleotide donors in chicken PGCs for performing small and defined sequence changes was investigated in this thesis. Specifically, homology-directed DNA repair (HDR) using oligonucleotide donors along with wild-type CRISPR/Cas9 (SpCas9-WT) or high fidelity CRISPR/Cas9 (SpCas9-HF1) was investigated in cultured chicken PGCs. The results obtained showed that small sequences changes ranging from a single to a few nucleotides could be precisely edited in many loci in chicken PGCs. In comparison to SpCas9-WT, SpCas9-HF1 increased the frequency of biallelic and single allele editing to generate specific homozygous and heterozygous genotypes. This finding demonstrates the utility of high fidelity CRISPR/Cas9 variants for performing sequence editing with high efficiency in PGCs. Since PGCs can be converted into pluripotent stem cells that can potentially differentiate into many cell types from the three germ layers, genome editing of PGCs can, therefore, be used to generate PGC-derived avian cell types with defined genetic alterations to investigate the host-pathogen interactions of infectious avian diseases. To investigate this possibility, the chicken ANP32A gene was investigated as a target for genetic resistance to avian influenza virus in PGC-derived chicken cell lines. Targeted modification of ANP32A was performed to generate clonal lines of genome-edited PGCs. Avian influenza minigenome replication assays were subsequently performed in the ANP32A-mutant PGC-derived cell lines. The results verified that ANP32A function is crucial for the function of both avian virus polymerase and human-adapted virus polymerase in chicken cells. Importantly, an asparagine to isoleucine mutation at position 129 (N129I) in chicken ANP32A failed to support avian influenza polymerase function. This genetic change can be introduced into chickens and validated in virological studies. Importantly, the results of my investigation demonstrate the potential to use genome editing of PGCs as an approach to generate many types of unique cell models for the study of avian biology. Genome editing of PGCs may also be applied to unravel the genes that control the development of the avian germ cell lineage. In the mouse, gene targeting has been extensively applied to generate loss-of-function mouse models to use the reverse genetics approach to identify key genes that regulate the migration of specified PGCs to the genital ridges. Avian PGCs express similar cytokine receptors as their mammalian counterparts. However, the factors guiding the migration of avian PGCs are largely unknown. To address this, CRISPR/Cas9 was used in this thesis to generate clonal lines of chicken PGCs with loss-of-function deletions in the CXCR4 and c-Kit genes which have been implicated in controlling mouse PGC migration. The results showed that CXCR4-deficient PGCs are absent from the gonads whereas c-Kit-deficient PGCs colonise the developing gonads in reduced numbers and are significantly reduced or absent from older stages. This finding shows a conserved role for CXCR4 and c-Kit signalling in chicken PGC development. Importantly, other genes suspected to be involved in controlling the development of avian germ cells can be investigated using this approach to increase our understanding of avian reproductive biology. Finally, the methods developed in this thesis for editing of the chicken genome may be applied in other avian species once culture methods for the PGCs from these species are develope