Chromatin proteins and RNA are associated with DNA during all phases of mitosis.

Mitosis brings about major changes to chromosome and nuclear structure. We used recently developed proximity ligation assay-based techniques to investigate the association with DNA of chromatin-associated proteins and RNAs in Drosophila embryos during mitosis. All groups of tested proteins, histone-modifying and chromatin-remodeling proteins and methylated histones remained in close proximity to DNA during all phases of mitosis. We also found that RNA transcripts are associated with DNA during all stages of mitosis. Reduction of H3K27me3 levels or elimination of RNAs had no effect on the association of the components of PcG and TrxG complexes to DNA. Using a combination of proximity ligation assay-based techniques and super-resolution microscopy, we found that the number of protein-DNA and RNA-DNA foci undergoes significant reduction during mitosis, suggesting that mitosis may be accompanied by structural re-arrangement or compaction of specific chromatin domains

Evaluating factor structure and instrument stability through measurement invariance of the DECA, second edition

In the process of instrument development, developers follow protocols and conduct analyses to ensure psychometric properties are met. During development, developers determine an assessment format that best aligns to their desired construct, including direct or indirect assessment. Within indirect assessment, participants hold a non-active role in the assessment process, where a separate informant supports the assessment process on behalf of the participant. Within this type of assessment, informant perception, being implicit and explicit biases, as well as informant memory implicate the results of the instrument; and therefore, the psychometric properties. This study sought to understand the factor structure and instrument stability via measurement invariance of the Devereux Early Childhood Assessment (DECA), second edition, within a sample of children enrolled in Head Start. Measurement invariance seeks to measure stability within populations to ensure the instrument is equivalent between groups. Further, achieving invariance within instruments means interpretations in observed change reflect actual change within the latent variable (Millsap, 2010). Exploratory and confirmatory factor analysis identified a four-factor structure. Most of the items within the total protective factors domain aligned to the factor structure described by the DECA. Six of those items cross-loaded; 9 of the 11 items within behavior concerns domain loaded to a factor within the total protective factors domain. Within measurement invariance, gender, race/ethnicity, dual language status, and time variables were examined. No invariance model met configural invariance. To further examine invariance by gender, items within the behavior concerns domain were excluded. Configural and metric invariance were met and partial invariance within strong and strict invariance were met. This notes the need to further examine the items included in the behavior concerns domain. Based on the results of this study, the argument that conducting reliability and validity analyses during instrument developer is insufficient. Developers should conduct more advanced analyses to ensure robustness and appropriateness within the population(s) for which the instrument has been devised. Finally, due to the nature of indirect assessment, these analyses are vitally important due to the potential error that may be imparted into an informant's judgement via perception and memory

Physicians\u27 Insurance Limits and Malpractice Payments: Evidence from Texas Closed Claims, 1990-2003

Physicians\u27 insuring practices influence their incentives to take care when treating patients, their risk of making out-of-pocket payments in malpractice cases, and the adequacy of compensation available to injured patients. Yet, these practices and their effects have rarely been studied. Using Texas Department of Insurance data on 9,525 paid malpractice claims against physicians that closed 1990-2003, we provide the first systematic evidence on levels of coverage purchased by physicians with paid liability claims and how those levels affect out-of-pocket payments and patient compensation. We find that these physicians carried much less insurance than is conventionally believed, that their real primary limits declined steadily over time, that policy limits often act as effective caps on recovery, and that personal contributions by physicians to close claims were rare. Our findings call into question a number of common assumptions about the relationship between physician insuring practices and the medical malpractice liability system. For a shorter, summary version of this research, see Charles Silver, Kathryn Zeiler, Bernard Black, David Hyman & William Sage, Malpractice Payouts and Malpractice Insurance: Evidence from Texas Closed Claims, 1990-2003, Geneva Papers on Risk and Insurance yyy-zzz (forthcoming 2008), available at http://ssrn.com/abstract=983199

An investigation into the roles of p53, Nodal/ Activin and fibroblast growth factor signalling in early heart development

The work presented in this thesis is an investigation into the roles of p53, Nodal/ Activin and fibroblast growth factor (FGF) signalling in early heart development in the model organism Xenopus laevis. The first step of heart development is the specification of cardiac tissue. However, the timing of cardiac specification and the signals which control it are largely unknown. The Nodal/ Activin and FGF signalling pathways have been implicated in cardiac specification but there is little evidence demonstrating a direct role for these pathways. Using soluble molecular inhibitors of the Nodal/ Activin and FGF signalling pathways at different stages of development, the effects of time-controlled inhibition on cardiac progenitor cells and differentiated cardiac tissue were observed. Nodal/ Activin signalling was found to be required for cardiac specification during a 2-3 hour time window following midblastula transition. It was shown that FGF signalling is not required prior to gastrulation for cardiac specification, but is required later for normal heart development. It was hypothesised that p53 may be involved in cardiac specification by mediating crosstalk between the Nodal/ Activin and FGF signalling pathways, in a similar manner to its previously suggested role in mesoderm induction. Using a combination of p53 antisense morpholino oligonucleotides and a dominant negative p53 protein, the effects of p53 downregulation on cardiac progenitor cells and differentiated cardiac tissue were examined. A novel role for p53 in early heart development was found. These findings contribute to an understanding of how p53, Nodal/ Activin and FGF signalling orchestrate numerous developmental events in the early embryo. This knowledge will be useful to advance our understanding of congenital heart diseases and for the development of improved directed differentiation protocols for cardiac regenerative medicine

Do Defendants Pay What Juries Award? Post-Verdict Haircuts in Texas Medical Malpractice Cases, 1988–2003

Legal scholars, legislators, policy advocates, and the news media frequently use jury verdicts to draw conclusions about the performance of the tort system. However, actual payouts can differ greatly from verdicts. We report evidence on post-verdict payouts from the most comprehensive longitudinal study of matched jury verdicts and payouts. Using data on all insured medical malpractice claims in Texas from 1988–2003 in which the plaintiff received at least $25,000 (in 1988 dollars) following a jury trial, we find that most jury awards received “haircuts.” Seventy-five percent of plaintiffs received a payout less than the adjusted verdict (jury verdict plus prejudgment and postjudgment interest), 20 percent received the adjusted verdict (within ± 2 percent), and 5 percent received more than the adjusted verdict. Overall, plaintiffs received a mean (median) per-case haircut of 29 percent (19 percent), and an aggregate haircut of 56 percent, relative to the adjusted verdict. The larger the verdict, the more likely and larger the haircut. For cases with a positive adjusted verdict under$100,000, 47 percent of plaintiffs received a haircut, with a mean (median) per-case haircut of 8 percent (2 percent). For cases with an adjusted verdict larger than $2.5 million, 98 percent of plaintiffs received a haircut with a mean (median) per-case haircut of 56 percent (61 percent). Insurance policy limits are the most important factor in explaining haircuts. Caps on damages in death cases and caps on punitive damages are also important, but defendants often paid substantially less than the adjusted allowed verdict. Remittitur accounts for a small percentage of the haircuts. Punitive damage awards have only a small effect on payouts. Out-of-pocket payments by physicians are rare, never large, and usually unrelated to punitive damage awards. Most cases settle, presumably in the shadow of the outcome if the case were to be tried. That outcome is not the jury award, but the actual post-verdict payout. Because defendants rarely pay what juries award, jury verdicts alone do not provide a sufficient basis for claims about the performance of the tort system

Physical and digital architecture for collection and analysis of imparted accelerations on Zip Line attractions

The accelerations experienced by riders of Zip Line attractions is an underexplored area of public safety assurance. These amusement devices require complex processes to collect and analyze acceleration data. Highly versatile and effective rider-worn and ride-carried devices are necessary to collect acceleration and velocity data without affecting the integrity of the ride. This paper introduces the use of a sensor device for collecting Zip Line acceleration data in the form of a Trailing Trolley. This architecture extends the work of Sicat et. al.’s which proposed the use of a Sensor Vest and Headwear to collect linear and rotational accelerations of a Zip Line rider. We investigate the logistics of combining the two sensor platforms and formulate a procedure to post-process and analyze the data. Techniques to extract, filter, and process the accelerations recorded is discussed and the potential for the synthesis of positioning linear and rotational data is described. Additional testing of data collection and analysis is necessary to prove the viability of these techniques and apparatuses as potential parts of a standardized test method for measuring rider experienced g-forces on Zip Lines

Treatment initiation among persons diagnosed with drug resistant tuberculosis in Johannesburg, South Africa

In South Africa, roughly half of the drug-resistant TB cases diagnosed are reported to have been started on treatment. We determined the proportion of persons diagnosed with rifampicin resistant (RR-) TB who initiated treatment in Johannesburg after the introduction of decentralized RR-TB care in 2011