Histone deacetylase adaptation in single ventricle heart disease and a young animal model of right ventricular hypertrophy.

BackgroundHistone deacetylase (HDAC) inhibitors are promising therapeutics for various forms of cardiac diseases. The purpose of this study was to assess cardiac HDAC catalytic activity and expression in children with single ventricle (SV) heart disease of right ventricular morphology, as well as in a rodent model of right ventricular hypertrophy (RVH).MethodsHomogenates of right ventricle (RV) explants from non-failing controls and children born with a SV were assayed for HDAC catalytic activity and HDAC isoform expression. Postnatal 1-day-old rat pups were placed in hypoxic conditions, and echocardiographic analysis, gene expression, HDAC catalytic activity, and isoform expression studies of the RV were performed.ResultsClass I, IIa, and IIb HDAC catalytic activity and protein expression were elevated in the hearts of children born with a SV. Hypoxic neonatal rats demonstrated RVH, abnormal gene expression, elevated class I and class IIb HDAC catalytic activity, and protein expression in the RV compared with those in the control.ConclusionsThese data suggest that myocardial HDAC adaptations occur in the SV heart and could represent a novel therapeutic target. Although further characterization of the hypoxic neonatal rat is needed, this animal model may be suitable for preclinical investigations of pediatric RV disease and could serve as a useful model for future mechanistic studies

New development: Directly elected mayors in Italy: creating a strong leader doesn’t mean creating strong leadership

More than 20 years after their introduction, directly elected mayors are key players in Italian urban governance. This article explains the main effects of this reform on local government systems and provides lessons for other countries considering directly elected mayors

Effects of Level of Effort Measurement in the Application of Earned Value Management

Major Air Force contracts are subject to overview utilizing Earned Value Management (EVM). EVM is flexible in its application through the adherence of guidelines rather than strict rules. Due to this method, there is concern for potential abuse of application through overuse of Level of Effort (LOE) as a measurement technique. There are current recommended practices and rules of thumb that suggest LOE should be limited to 15% of a program’s budget with no quantitative research to support this claim. This study examines how LOE is currently employed in ACAT I Air Force programs and what LOE’s impact is on a program’s performance. This is done using data from integrated program management reports (IPMRs) found within the EVM Central Repository (EVM-CR) database and employing descriptive analysis with bivariate and multivariate inferential analysis. Results show there is likely slight influence from the 15% guideline, but LOE application varies widely from 0% to 100%. The actual effect from LOE on a program is found to be nonexistent showing no performance-based reason to be concerned with the amount of LOE utilized. This finding would call for reexamination of recommended guidelines concerning LOE and potentially removing unnecessary limitations of EVM applicatio

An Exploration of the Relationship between Adolescent Adjustment to Diabetes Mellitus and Parent-Child Relationship Problems

The focus of this study is on adolescents who have diabetes mellitus and their adjustment to that disease. This study explores the relationship between adolescent adjustment to diabetes mellitus and the parent-child relationship. Erik Erikson\u27s Theory of Cognitive Development served as the theoretical framework for the study. The study utilized descriptive methodology. Data was collected using Child\u27s Attitude Toward Mother Scale and Child\u27s Attitude Toward Father Scale, the Diabetic Adjustment Scale, and a researcher developed structured\u27interview. The study population was ten families each with a diabetic adolescent for the study. Individual case scores and correlation statistics were used to describe the data. A limitation of the study was use of a small, non-random sample. Results of the study indicated that if the adolescent experienced problems adjusting to diabetes mellitus, as measured tpy a score on the Diabetic Adjustment Scale, there were problems in the adolescent\u27s relationship with his or her parent

Magnetars as Astrophysical Laboratories of Extreme Quantum Electrodynamics: The Case for a Compton Telescope

A next generation of Compton and pair telescopes that improve MeV-band detection sensitivity by more than a decade beyond current instrumental capabilities will open up new insights into a variety of astrophysical source classes. Among these are magnetars, the most highly magnetic of the neutron star zoo, which will serve as a prime science target for a new mission surveying the MeV window. This paper outlines the core questions pertaining to magnetars that can be addressed by such a technology. These range from global magnetar geometry and population trends, to incisive probes of hard X-ray emission locales, to providing cosmic laboratories for spectral and polarimetric testing of exotic predictions of QED, principally the prediction of the splitting of photons and magnetic pair creation. Such fundamental physics cannot yet be discerned in terrestrial experiments. State of the art modeling of the persistent hard X-ray tail emission in magnetars is presented to outline the case for powerful diagnostics using Compton polarimeters. The case highlights an inter-disciplinary opportunity to seed discovery at the interface between astronomy and physics.Comment: 11 pages, 4 figures, Astro2020 Science White Paper submitted to the National Academies of Science

Linear-Accelerator Program

Contains reports on one research project

First narrow-band search for continuous gravitational waves from known pulsars in advanced detector data

Spinning neutron stars asymmetric with respect to their rotation axis are potential sources of continuous gravitational waves for ground-based interferometric detectors. In the case of known pulsars a fully coherent search, based on matched filtering, which uses the position and rotational parameters obtained from electromagnetic observations, can be carried out. Matched filtering maximizes the signalto- noise (SNR) ratio, but a large sensitivity loss is expected in case of even a very small mismatch between the assumed and the true signal parameters. For this reason, narrow-band analysis methods have been developed, allowing a fully coherent search for gravitational waves from known pulsars over a fraction of a hertz and several spin-down values. In this paper we describe a narrow-band search of 11 pulsars using data from Advanced LIGO’s first observing run. Although we have found several initial outliers, further studies show no significant evidence for the presence of a gravitational wave signal. Finally, we have placed upper limits on the signal strain amplitude lower than the spin-down limit for 5 of the 11 targets over the bands searched; in the case of J1813-1749 the spin-down limit has been beaten for the first time. For an additional 3 targets, the median upper limit across the search bands is below the spin-down limit. This is the most sensitive narrow-band search for continuous gravitational waves carried out so far

Acute Changes in Sleep Duration on Eating Behaviors and Appetite-Regulating Hormones in Overweight/Obese Adults

There is considerable interest in the role of sleep in weight regulation, yet few studies have examined this relationship in overweight/obese (OW/OB) adults. Using a within-subject, counterbalanced design, 12 OW/OB women were studied in lab with two nights of short (5 hr time in bed [TIB]) and two nights of long (9 hr TIB) sleep. Hunger, consumption at a buffet, and fasting hormone levels were obtained. Significant polysomnographic differences occurred between conditions in total sleep time and sleep architecture (ps < .001). Percent energy from protein at the buffet increased following short sleep. No differences were observed for total energy intake or measured hormones. Further research is needed to determine how lengthening sleep impacts weight regulation in OW/OB adults

Proof-theoretic semantics, a problem with negation and prospects for modality

This paper discusses proof-theoretic semantics, the project of specifying the meanings of the logical constants in terms of rules of inference governing them. I concentrate on Michael Dummett’s and Dag Prawitz’ philosophical motivations and give precise characterisations of the crucial notions of harmony and stability, placed in the context of proving normalisation results in systems of natural deduction. I point out a problem for defining the meaning of negation in this framework and prospects for an account of the meanings of modal operators in terms of rules of inference

Going Solo: findings from a survey of women ageing without a partner and who do not have children

Greater longevity in the UK population has led to the increasing diversity of women experiencing ageing in a multitude of ways. Internationally gender inequalities within ageing are still relatively invisible within both government policy and everyday life for particular groups of women. This paper explores the concept of women growing older ‘solo’ by which we mean women who find themselves non partnered and ageing without children as they move into later life. We report on the findings from a mixed-methods survey of 76 solo women in the UK aged 50 years and over, used to provide a broader overview of the issues and challenges they face as they move into later life. Qualitative data from the survey captured respondents’ perspectives about the links between their relationships status and wellbeing in later life and highlighted specific cumulative disadvantages emerging for some women as a result of their solo lifestyles. We discuss two key themes were identified; ‘solo-loneliness’ and ‘meaningful futures’ in conjunction with the relevant literature and make suggestions for future research within gender and ageing studies that could enhance more positive approaches to solo lifestyles