A twist in the geometry of rotating black holes: seeking the cause of acausality

We investigate Kerr-Newman black holes in which a rotating charged ring-shaped singularity induces a region which contains closed timelike curves (CTCs). Contrary to popular belief, it turns out that the time orientation of the CTC is opposite to the direction in which the singularity or the ergosphere rotates. In this sense, CTCs "counter-rotate" against the rotating black hole. We have similar results for all spacetimes sufficiently familiar to us in which rotation induces CTCs. This motivates our conjecture that perhaps this counter-rotation is not an accidental oddity particular to Kerr-Newman spacetimes, but instead there may be a general and intuitively comprehensible reason for this.Comment: 21 pages, 5 figures; replaced to match published version forthcoming in General Relativity and Gravitatio

Medical Providers\u27 Use of Maternal Mental Health Screening Tools During Prenatal Appointments in Southeast Georgia

In the United States, maternal mental health disorders are the most common comorbidities experienced during pregnancy and after childbirth. In particular, the state of Georgia reports that 1 in 7 Georgian mothers experience depression, anxiety, obsessive-compulsive disorders, or psychosis related to these disorders. Research suggests that untreated maternal mental health can have adverse effects on the mother and unborn child. Conditions such as autism, mixed handedness, reduced cognitive ability, and affective disorders can develop while the child is in the womb of a depressed mother. Routine maternal mental health screening using a validated screening tool has been recommended to help mitigate this risk. However, adherence to this recommendation is unknown. The purpose of this qualitative study is to explore medical providers\u27 use of maternal mental health screening tools during prenatal appointments and identify barriers and facilitators to routine screening implementation. Online open-ended surveys were completed by 20 medical providers, and 8 agreed to optional follow-up telephone interviews. They were recruited through a homogeneous purposive, snowball, and convenience sampling method. Qualitative content analysis was used to summarize and interpret the data. The following main categories emerged from the data: current screening practices, reason for screening tool selection, outcomes of screening, inefficiencies in screening process, challenges in treatment evaluation, and perceived value for mental health screening recommendations. Categories for barriers to screening included limited knowledge and understanding of mental health and limited resources to support mental health screening. While facilitators to screening included, support structures and development of knowledge, skills, and techniques, and emerged from the data. Findings from this study can inform screening tool implementation techniques which reduce barriers and promotes facilitators experienced by medical providers during prenatal appointments. Additionally, findings can inform the development of standardized screening guidelines to support screening tool utilization by providers. INDEX WORDS: Maternal mental health, Mental health screening tool, Medical providers, Prenatal, Perinatal, Southeast Georgia, Normalization Process Theor

Exploring and Changing Cognitive Representations, Coping and Quality Of Life Outcomes in Chronic Spontaneous Urticaria

Chronic Spontaneous Urticaria (CU) is a pruritic skin disorder that affects 0.8% of the population. As its aetiology is not fully understood the aim is to control symptoms through medicines to improve quality of life (QoL). Demographic and clinical factors have been inconsistent and poorly predict QoL but one modifiable factor that has gained credence is ones illness representations. The Common-Sense Model (Leventhal, Meyer and Nerenz, 1980) postulates that these guide coping procedures that impact outcomes. The aim of the thesis was to examine whether CU representations (mediated by coping) predicted QoL and whether both representations and QoL in CU were amenable to change via intervention. Preliminary studies undertaken validated CSM measures in CU and confirmed key reference values for CU-related QoL and its measurement. CU was seen as uncontrollable, emotionally arousing, chronic, cyclical, caused by stress and immunity with serious consequences and has a moderate impact on QoL (n=78). The necessity to take CU medicines equalled concerns about side effects. Cognitive representations were the strongest predictors of QoL explaining 35.0-60.6% of the variance independent of coping. Qualitative analyses presented CU as unsightly, uncontrollable and difficult to comprehend and self-regulate. Fifteen participants undertook psych-education and action plans to change CU representations. Multivariate analyses found a strong within-group main effect on QoL outcomes (p<.001) and for aspects of outcome over time (all p<.001). Correlation based change analysis further inferred that targeting CU cognitions resulted in changing QoL outcomes over time. In summary the thesis supported that: poor QoL is prevalent in individuals experiencing CU. Not only do CU representations predict QoL outcomes, they are amenable to change via intervention as are QoL outcomes. Such findings have implications for CU-related QoL research and how health psychology-dermatology collaborations maybe instrumental to improving outcome through psycho-education interventions in routine care to facilitate better CU self-management

Angiotensin Receptor Neprilysin Inhibition Compared With Enalapril on the Risk of Clinical Progression in Surviving Patients With Heart Failure

BACKGROUND: -Clinical trials in heart failure have focused on the improvement in symptoms or decreases in the risk of death and other cardiovascular events. Little is known about the effect of drugs on the risk of clinical deterioration in surviving patients. METHODS AND RESULTS: -We compared the angiotensin-neprilysin inhibitor LCZ696 (400 mg daily) with the angiotensinconverting enzyme inhibitor enalapril (20 mg daily) in 8399 patients with heart failure and reduced ejection fraction in a double-blind trial. The analyses focused on prespecified measures of nonfatal clinical deterioration. In comparison with the enalapril group, fewer LCZ696-treated patients required intensification of medical treatment for heart failure (520 versus 604; hazard ratio, 0.84; 95% confidence interval, 0.74-0.94; P=0.003) or an emergency department visit for worsening heart failure (hazard ratio, 0.66; 95% confidence interval, 0.52-0.85; P=0.001). The patients in the LCZ696 group had 23% fewer hospitalizations for worsening heart failure (851 versus 1079; P<0.001) and were less likely to require intensive care (768 versus 879; 18% rate reduction, P=0.005), to receive intravenous positive inotropic agents (31% risk reduction, P<0.001), and to have implantation of a heart failure device or cardiac transplantation (22% risk reduction, P=0.07). The reduction in heart failure hospitalization with LCZ696 was evident within the first 30 days after randomization. Worsening of symptom scores in surviving patients was consistently more common in the enalapril group. LCZ696 led to an early and sustained reduction in biomarkers of myocardial wall stress and injury (N-terminal pro-Btype natriuretic peptide and troponin) versus enalapril. CONCLUSIONS: -Angiotensin-neprilysin inhibition prevents the clinical progression of surviving patients with heart failure more effectively than angiotensin-converting enzyme inhibition. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01035255

Effect of remote ischemic conditioning on atrial fibrillation and outcome after coronary artery bypass grafting (RICO-trial)

Background: Pre- and postconditioning describe mechanisms whereby short ischemic periods protect an organ against a longer period of ischemia. Interestingly, short ischemic periods of a limb, in itself harmless, may increase the ischemia tolerance of remote organs, e.g. the heart (remote conditioning, RC). Although several studies have shown reduced biomarker release by RC, a reduction of complications and improvement of patient outcome still has to be demonstrated. Atrial fibrillation (AF) is one of the most common complications after coronary artery bypass graft surgery (CABG), affecting 27-46% of patients. It is associated with increased mortality, adverse cardiovascular events, and prolonged in-hospital stay. We hypothesize that remote ischemic pre- and/or post-conditioning reduce the incidence of AF following CABG, and improve patient outcome.Methods/design: This study is a randomized, controlled, patient and investigator blinded multicenter trial. Elective CABG patients are randomized to one of the following four groups: 1) control, 2) remote ischemic preconditioning, 3) remote ischemic postconditioning, or 4) remote ischemic pre- and postconditioning. Remote conditio

In vivo MRI and ex vivo histological assessment of the cardioprotection induced by ischemic preconditioning, postconditioning and remote conditioning in a closed-chest porcine model of reperfused acute myocardial infarction: importance of microvasculature

BACKGROUND: Cardioprotective value of ischemic post- (IPostC), remote (RIC) conditioning in acute myocardial infarction (AMI) is unclear in clinical trials. To evaluate cardioprotection, most translational animal studies and clinical trials utilize necrotic tissue referred to the area at risk (AAR) by magnetic resonance imaging (MRI). However, determination of AAR by MRI' may not be accurate, since MRI-indices of microvascular damage, i.e., myocardial edema and microvascular obstruction (MVO), may be affected by cardioprotection independently from myocardial necrosis. Therefore, we assessed the effect of IPostC, RIC conditioning and ischemic preconditioning (IPreC; positive control) on myocardial necrosis, edema and MVO in a clinically relevant, closed-chest pig model of AMI. METHODS AND RESULTS: Acute myocardial infarction was induced by a 90-min balloon occlusion of the left anterior descending coronary artery (LAD) in domestic juvenile female pigs. IPostC (6 x 30 s ischemia/reperfusion after 90-min occlusion) and RIC (4 x 5 min hind limb ischemia/reperfusion during 90-min LAD occlusion) did not reduce myocardial necrosis as assessed by late gadolinium enhancement 3 days after reperfusion and by ex vivo triphenyltetrazolium chloride staining 3 h after reperfusion, however, the positive control, IPreC (3 x 5 min ischemia/reperfusion before 90-min LAD occlusion) did. IPostC and RIC attenuated myocardial edema as measured by cardiac T2-weighted MRI 3 days after reperfusion, however, AAR measured by Evans blue staining was not different among groups, which confirms that myocardial edema is not a measure of AAR, IPostC and IPreC but not RIC decreased MVO. CONCLUSION: We conclude that IPostC and RIC interventions may protect the coronary microvasculature even without reducing myocardial necrosis

The Heart Is an Early Target of Anthrax Lethal Toxin in Mice: A Protective Role for Neuronal Nitric Oxide Synthase (nNOS)

Anthrax lethal toxin (LT) induces vascular insufficiency in experimental animals through unknown mechanisms. In this study, we show that neuronal nitric oxide synthase (nNOS) deficiency in mice causes strikingly increased sensitivity to LT, while deficiencies in the two other NOS enzymes (iNOS and eNOS) have no effect on LT-mediated mortality. The increased sensitivity of nNOS−/− mice was independent of macrophage sensitivity to toxin, or cytokine responses, and could be replicated in nNOS-sufficient wild-type (WT) mice through pharmacological inhibition of the enzyme with 7-nitroindazole. Histopathological analyses showed that LT induced architectural changes in heart morphology of nNOS−/− mice, with rapid appearance of novel inter-fiber spaces but no associated apoptosis of cardiomyocytes. LT-treated WT mice had no histopathology observed at the light microscopy level. Electron microscopic analyses of LT-treated mice, however, revealed striking pathological changes in the hearts of both nNOS−/− and WT mice, varying only in severity and timing. Endothelial/capillary necrosis and degeneration, inter-myocyte edema, myofilament and mitochondrial degeneration, and altered sarcoplasmic reticulum cisternae were observed in both LT-treated WT and nNOS−/− mice. Furthermore, multiple biomarkers of cardiac injury (myoglobin, cardiac troponin-I, and heart fatty acid binding protein) were elevated in LT-treated mice very rapidly (by 6 h after LT injection) and reached concentrations rarely reported in mice. Cardiac protective nitrite therapy and allopurinol therapy did not have beneficial effects in LT-treated mice. Surprisingly, the potent nitric oxide scavenger, carboxy-PTIO, showed some protective effect against LT. Echocardiography on LT-treated mice indicated an average reduction in ejection fraction following LT treatment in both nNOS−/− and WT mice, indicative of decreased contractile function in the heart. We report the heart as an early target of LT in mice and discuss a protective role for nNOS against LT-mediated cardiac damage