Estrogen and progesterone induce persistent increases in p53-dependent apoptosis and suppress mammary tumors in BALB/c-Trp53+/- mice

INTRODUCTION Treatment with estrogen and progesterone (E+P) mimics the protective effect of parity on mammary tumors in rodents and depends upon the activity of p53. The following experiments tested whether exogenous E+P primes p53 to be more responsive to DNA damage and whether these pathways confer resistance to mammary tumors in a mouse model of Li-Fraumeni syndrome. METHODS Mice that differ in p53 status (Trp53+/+, Trp53+/-, Trp53-/-) were treated with E+P for 14 days and then were tested for p53-dependent responses to ionizing radiation. Responses were also examined in parous and age-matched virgins. The effects of hormonal exposures on tumor incidence were examined in BALB/c-Trp53+/- mammary tissues. RESULTS Nuclear accumulation of p53 and apoptotic responses were increased similarly in the mammary epithelium from E+P-treated and parous mice compared with placebo and age-matched virgins. This effect was sustained for at least 7 weeks after E+P treatment and did not depend on the continued presence of ovarian hormones. Hormone stimulation also enhanced apoptotic responses to ionizing radiation in BALB/c-Trp53+/- mice but these responses were intermediate compared with Trp53+/+ and Trp-/- tissues, indicating haploinsufficiency. The appearance of spontaneous mammary tumors was delayed by parity in BALB/c-Trp53+/- mice. The majority of tumors lacked estrogen receptor (ER), but ER+ tumors were observed in both nulliparous and parous mice. However, apoptotic responses to ionizing radiation and tumor incidence did not differ among outgrowths of epithelial transplants from E+P-treated donors and nulliparous donors. CONCLUSION Therefore, E+P and parity confer a sustained increase in p53-mediated apoptosis within the mammary epithelium and suppress mammary tumorigenesis, but this effect was not retained in epithelial outgrowths.This work was supported by grants from the US Army Medical Research and Materiel Command (W81XWH0410385 to KAD and DAMD17-01-1-0315 to ACB) and the National Institutes of Health (RO1-CA095164 to DJJ)

High magnetic field studies of the Vortex Lattice structure in YBa2Cu3O7

We report on small angle neutron scattering measurements of the vortex lattice in twin-free YBa2Cu3O7, extending the previously investigated maximum field of 11~T up to 16.7~T with the field applied parallel to the c axis. This is the first microscopic study of vortex matter in this region of the superconducting phase. We find the high field VL displays a rhombic structure, with a field-dependent coordination that passes through a square configuration, and which does not lock-in to a field-independent structure. The VL pinning reduces with increasing temperature, but is seen to affect the VL correlation length even above the irreversibility temperature of the lattice structure. At high field and temperature we observe a melting transition, which appears to be first order, with no detectable signal from a vortex liquid above the transition

Bioelectronic DNA detection of human papillomaviruses using eSensor™: a model system for detection of multiple pathogens

BACKGROUND: We used human papillomaviruses (HPV) as a model system to evaluate the utility of a nucleic acid, hybridization-based bioelectronic DNA detection platform (eSensor™) in identifying multiple pathogens. METHODS: Two chips were spotted with capture probes consisting of DNA oligonucleotide sequences specific for HPV types. Electrically conductive signal probes were synthesized to be complementary to a distinct region of the amplified HPV target DNA. A portion of the HPV L1 region that was amplified by using consensus primers served as target DNA. The amplified target was mixed with a cocktail of signal probes and added to a cartridge containing a DNA chip to allow for hybridization with complementary capture probes. RESULTS: Two bioelectric chips were designed and successfully detected 86% of the HPV types contained in clinical samples. CONCLUSIONS: This model system demonstrates the potential of the eSensor platform for rapid and integrated detection of multiple pathogens

Effect of sprint approach velocity and distance on deceleration performance in NCAA Division I female softball athletes

Team sports require athletes to rapidly reduce whole body momentum and velocity, to efficiently change direction, or to avoid defenders. Decelerations often occur following varying approach distances and velocities. The aim of this study was to investigate the effects of different sprinting approach distances, and therefore velocities and momenta on measures of horizontal deceleration performance within female NCAA Division I softball players. Athletes performed an acceleration:deceleration assessment (ADA) over 20 yards (18.29 m) (ADA20) and 10 yards (9.14 m) (ADA10), respectively. The sample was divided into high and low performance groups for approach velocity and approach momentum, and between-group differences were studied for each test. Correlations between measures of deceleration were analysed between the ADA10 and ADA20. Results suggested that during the ADA20 trials, athletes initiated the deceleration phase at greater approach velocities (p < .001, ES = 2.71) and momenta (p < .001, ES = 2.65), generating greater reductions in velocity (p < .001, ES = 1.60) and momentum (p < .001, ES = 1.50). Within the ADA10, athletes within the high velocity group saw significantly greater reductions in velocity (p = .009, ES = 1.24). This was not observed within the ADA20. A significant negative association was found between average deceleration within the ADA10 and ADA20 (r = -0.443, p = .039). Findings suggest that horizontal decelerations are influenced by the approach distance, velocity, and momentum, which athletes are exposed to before initiating the deceleration phase. This should be accounted for when implementing training to enhance such qualities

Broadening the Debate About Post-trial Access to Medical Interventions: A Qualitative Study of Participant Experiences at the End of a Trial Investigating a Medical Device to Support Type 1 Diabetes Self-Management.

Increasing ethical attention and debate is focusing on whether individuals who take part in clinical trials should be given access to post-trial care. However, the main focus of this debate has been upon drug trials undertaken in low-income settings. To broaden this debate, we report findings from interviews with individuals (n = 24) who participated in a clinical trial of a closed-loop system, which is a medical device under development for people with type 1 diabetes that automatically adjusts blood glucose to help keep it within clinically recommended ranges. Individuals were recruited from UK sites and interviewed following trial close-out, at which point the closed-loop had been withdrawn. While individuals were stoical and accepting of the requirement to return the closed-loop, they also conveyed varying degrees of distress. Many described having relaxed diabetes management practices while using the closed-loop and having become deskilled as a consequence, which made reverting back to pre-trial regimens challenging. Participants also described unanticipated consequences arising from using a closed-loop. As well as deskilling, these included experiencing psychological and emotional benefits that could not be sustained after the closed-loop had been withdrawn and participants reevaluating their pre- and post-trial life in light of having used a closed-loop and now perceiving this life much more negatively. Participants also voiced frustrations about experiencing better blood glucose control using a closed-loop and then having to revert to using what they now saw as antiquated and imprecise self-management tools. We use these findings to argue that ethical debates about post-trial provisioning need to be broadened to consider potential psychological and emotional harms, and not just clinical harms, that may result from withdrawal of investigated treatments. We also suggest that individuals may benefit from information about potential nonclinical harms to help make informed decisions about trial participation.NIHR, JDR

Quasistationary binary inspiral. I. Einstein equations for the two Killing vector spacetime

The geometry of two infinitely long lines of mass moving in a fixed circular orbit is considered as a toy model for the inspiral of a binary system of compact objects due to gravitational radiation. The two Killing fields in the toy model are used, according to a formalism introduced by Geroch, to describe the geometry entirely in terms of a set of tensor fields on the two-manifold of Killing vector orbits. Geroch's derivation of the Einstein equations in this formalism is streamlined and generalized. The explicit Einstein equations for the toy model spacetime are derived in terms of the degrees of freedom which remain after a particular choice of gauge.Comment: 37 pages, REVTeX, one PostScript Figure included with epsfig; minor formatting changes and copyright notice added for journal publicatio

Towards diagnostic conversational profiles of patients presenting with dementia or functional memory disorders to memory clinics

Objective: This study explores whether the profile of patients' interactional behaviour in memory clinic conversations with a doctor can contribute to the clinical differentiation between functional memory disorders (FMD) and memory problems related to neurodegenerative diseases. Methods: Conversation Analysis of video recordings of neurologists' interactions with patients attending a specialist memory clinic. "Gold standard" diagnoses were made independently of CA findings by a multi-disciplinary team based on clinical assessment, neuropsychological testing and brain imaging. Results: Two discrete conversational profiles for patients with memory complaints emerged, including (i) who attends the clinic (i.e., whether or not patients are accompanied), and (ii) patients' responses to neurologists' questions about memory problems, such as difficulties with compound questions and providing specific and elaborated examples and frequent "I don't know" responses. Conclusion: Specific communicative difficulties are characteristic of the interaction patterns of patients with a neurodegenerative pathology. Those difficulties are manifest in memory clinic interactions with neurologists, thereby helping to differentiate patients with dementia from those with FMD. Practical implications: Our findings demonstrate that conversational profiles based on patients' contributions to memory clinic encounters have diagnostic potential to assist the screening and referral process from primary care, and the diagnostic service in secondary care

Explaining Agriculture Faculty Members’ Involvement in Study Abroad: Structural Relationships Among Personal - Dimension Variables

Agriculture faculty members’ involvement in study abroad programs can influence students’ participation in such. However, faculty members’ involvement may be limited by institutional, professional, and personal factors. This study was conducted to explain agriculture teaching faculty members’ involvement in study abroad programs by examining the structural relationships between their study abroad involvement and personal dimension variables. Results indicated the personal factors influencing faculty members’ involvement in study abroad include their perceptions of the knowledge, skill, and ability (KSA) outcomes of study abroad, awareness of study abroad programs and procedures, and prior international experience (PIE). The effect of faculty members’ perceptions of the KSA outcomes of study abroad programs on their involvement was mediated by their perceptions of the importance of those KSA outcomes for professionals in their field. Further, faculty members’ perceived importance of KSA outcomes was moderated by PIE. Recommendations for future practice include providing professional development and training to increase faculty members’ awareness of study abroad and increase opportunities for faculty members to gain international experiences. Future research should include replication of this study with agriculture faculty members at other institutions and the examination of relationships among professional and institutional dimension factor