216 research outputs found
Quasi-Normal Modes of Stars and Black Holes
Perturbations of stars and black holes have been one of the main topics of
relativistic astrophysics for the last few decades. They are of particular
importance today, because of their relevance to gravitational wave astronomy.
In this review we present the theory of quasi-normal modes of compact objects
from both the mathematical and astrophysical points of view. The discussion
includes perturbations of black holes (Schwarzschild, Reissner-Nordstr\"om,
Kerr and Kerr-Newman) and relativistic stars (non-rotating and
slowly-rotating). The properties of the various families of quasi-normal modes
are described, and numerical techniques for calculating quasi-normal modes
reviewed. The successes, as well as the limits, of perturbation theory are
presented, and its role in the emerging era of numerical relativity and
supercomputers is discussed.Comment: 74 pages, 7 figures, Review article for "Living Reviews in
Relativity
A systematic review of intervention effects on potential mediators of children\u27s physical activity
Background : Many interventions aiming to increase children’s physical activity have been developed and implemented in a variety of settings, and these interventions have previously been reviewed; however the focus of these reviews tends to be on the intervention effects on physical activity outcomes without consideration of the reasons and pathways leading to intervention success or otherwise. To systematically review the efficacy of physical activity interventions targeting 5-12 year old children on potential mediators and, where possible, to calculate the size of the intervention effect on the potential mediator. Methods : A systematic search identified intervention studies that reported outcomes on potential mediators of physical activity among 5-12 year old children. Original research articles published between 1985 and April 2012 were reviewed. Results : Eighteen potential mediators were identified from 31 studies. Positive effects on cognitive/psychological potential mediators were reported in 15 out of 31 studies. Positive effects on social environmental potential mediators were reported in three out of seven studies, and no effects on the physical environment were reported. Although no studies were identified that performed a mediating analysis, 33 positive intervention effects were found on targeted potential mediators (with effect sizes ranging from small to large) and 73% of the time a positive effect on the physical activity outcome was reported. Conclusions : Many studies have reported null intervention effects on potential mediators of children’s physical activity; however, it is important that intervention studies statistically examine the mediating effects of interventions so the most effective strategies can be implemented in future programs
Anti-angiogenic therapy for cancer: Current progress, unresolved questions and future directions
Tumours require a vascular supply to grow and can achieve this via the expression of pro-angiogenic growth factors, including members of the vascular endothelial growth factor (VEGF) family of ligands. Since one or more of the VEGF ligand family is overexpressed in most solid cancers, there was great optimism that inhibition of the VEGF pathway would represent an effective anti-angiogenic therapy for most tumour types. Encouragingly, VEGF pathway targeted drugs such as bevacizumab, sunitinib and aflibercept have shown activity in certain settings. However, inhibition of VEGF signalling is not effective in all cancers, prompting the need to further understand how the vasculature can be effectively targeted in tumours. Here we present a succinct review of the progress with VEGF-targeted therapy and the unresolved questions that exist in the field: including its use in different disease stages (metastatic, adjuvant, neoadjuvant), interactions with chemotherapy, duration and scheduling of therapy, potential predictive biomarkers and proposed mechanisms of resistance, including paradoxical effects such as enhanced tumour aggressiveness. In terms of future directions, we discuss the need to delineate further the complexities of tumour vascularisation if we are to develop more effective and personalised anti-angiogenic therapies. © 2014 The Author(s)
Genetic spectrum of hereditary neuropathies with onset in the first year of life
Early onset hereditary motor and sensory neuropathies are rare disorders encompassing congenital hypomyelinating neuropathy with disease onset in the direct post-natal period and Dejerine–Sottas neuropathy starting in infancy. The clinical spectrum, however, reaches beyond the boundaries of these two historically defined disease entities. De novo dominant mutations in PMP22, MPZ and EGR2 are known to be a typical cause of very early onset hereditary neuropathies. In addition, mutations in several other dominant and recessive genes for Charcot–Marie–Tooth disease may lead to similar phenotypes. To estimate mutation frequencies and to gain detailed insights into the genetic and phenotypic heterogeneity of early onset hereditary neuropathies, we selected a heterogeneous cohort of 77 unrelated patients who presented with symptoms of peripheral neuropathy within the first year of life. The majority of these patients were isolated in their family. We performed systematic mutation screening by means of direct sequencing of the coding regions of 11 genes: MFN2, PMP22, MPZ, EGR2, GDAP1, NEFL, FGD4, MTMR2, PRX, SBF2 and SH3TC2. In addition, screening for the Charcot–Marie–Tooth type 1A duplication on chromosome 17p11.2-12 was performed. In 35 patients (45%), mutations were identified. Mutations in MPZ, PMP22 and EGR2 were found most frequently in patients presenting with early hypotonia and breathing difficulties. The recessive genes FGD4, PRX, MTMR2, SBF2, SH3TC2 and GDAP1 were mutated in patients presenting with early foot deformities and variable delay in motor milestones after an uneventful neonatal period. Several patients displaying congenital foot deformities but an otherwise normal early development carried the Charcot–Marie–Tooth type 1A duplication. This study clearly illustrates the genetic heterogeneity underlying hereditary neuropathies with infantile onset
Cardio-metabolic risk in 5-year-old children prenatally exposed to maternal psychosocial stress: the ABCD study
<p>Abstract</p> <p>Background</p> <p>Recent evidence, both animal and human, suggests that modifiable factors during fetal and infant development predispose for cardiovascular disease in adult life and that they may become possible future targets for prevention. One of these factors is maternal psychosocial stress, but so far, few prospective studies have been able to investigate the longer-term effects of stress in detail, i.e. effects in childhood. Therefore, our general aim is to study whether prenatal maternal psychosocial stress is associated with an adverse cardio-metabolic risk profile in the child at age five.</p> <p>Methods/design</p> <p>Data are available from the Amsterdam Born Children and their Development (ABCD) study, a prospective birth cohort in the Netherlands. Between 2003-2004, 8,266 pregnant women filled out a questionnaire including instruments to determine anxiety (STAI), pregnancy related anxiety (PRAQ), depressive symptoms (CES-D), parenting stress (PDH scale) and work stress (Job Content Questionnaire).</p> <p>Outcome measures in the offspring (age 5-7) are currently collected. These include lipid profile, blood glucose, insulin sensitivity, body composition (body mass index, waist circumference and bioelectrical impedance analysis), autonomic nervous system activity (parasympathetic and sympathetic measures) and blood pressure.</p> <p>Potential mediators are maternal serum cortisol, gestational age and birth weight for gestational age (intrauterine growth restriction). Possible gender differences in programming are also studied.</p> <p>Discussion</p> <p>Main strengths of the proposed study are the longitudinal measurements during three important periods (pregnancy, infancy and childhood), the extensive measurement of maternal psychosocial stress with validated questionnaires and the thorough measurement of the children's cardio-metabolic profile. The availability of several confounding factors will give us the opportunity to quantify the independent contribution of maternal stress during pregnancy to the cardio-metabolic risk profile of her offspring. Moreover, the mediating role of maternal cortisol, intrauterine growth, gestational age and potential gender differences can be explored extensively. If prenatal psychosocial stress is indeed found to be associated with the offspring's cardio-metabolic risk, these results support the statement that primary prevention of cardiovascular disease may start even before birth by reducing maternal stress during pregnancy.</p
The relationship between basal and acute HPA axis activity and aggressive behavior in adults
The hypothalamic–pituitary–adrenal (HPA) axis seems to play a major role in the development, elicitation, and enhancement of aggressive behavior in animals. Increasing evidence suggests that this is also true for humans. However, most human research on the role of the HPA axis in aggression has been focusing on highly aggressive children and adolescent clinical samples. Here, we report on a study of the role of basal and acute HPA axis activity in a sample of 20 healthy male and female adults. We used the Taylor Aggression Paradigm to induce and measure aggression. We assessed the cortisol awakening response as a trait measure of basal HPA axis activity. Salivary free cortisol measures for the cortisol awakening response were obtained on three consecutive weekdays immediately following awakening and 30, 45, and 60 min after. Half of the subjects were provoked with the Taylor Aggression Paradigm to behave aggressively; the other half was not provoked. Acute HPA axis activity was measured four times, once before and three times after the induction of aggression. Basal cortisol levels were significantly and negatively related to aggressive behavior in the provoked group and explained 67% of the behavioral variance. Cortisol levels following the induction of aggression were significantly higher in the provoked group when baseline levels were taken into account. The data implicate that the HPA axis is not only relevant to the expression of aggressive behavior in clinical groups, but also to a large extent in healthy ones
Prenatal Stress and Balance of the Child's Cardiac Autonomic Nervous System at Age 5-6 Years
Objective: Autonomic nervous system (ANS) misbalance is a potential causal factor in the development of cardiovascular disease. The ANS may be programmed during pregnancy due to various maternal factors. Our aim is to study maternal prenatal psychosocial stress as a potential disruptor of cardiac ANS balance in the child. Methods: Mothers from a prospective birth cohort (ABCD study) filled out a questionnaire at gestational week 16 [IQR 12– 20], that included validated instruments for state anxiety, depressive symptoms, pregnancy-related anxiety, parenting daily hassles and job strain. A cumulative stress score was also calculated (based on 80 th percentiles). Indicators of cardiac ANS in the offspring at age 5–6 years are: pre-ejection period (PEP), heart rate (HR), respiratory sinus arrhythmia (RSA) and cardiac autonomic balance (CAB), measured with electrocardiography and impedance cardiography in resting supine and sitting positions. Results: 2,624 mother-child pairs, only single births, were available for analysis. The stress scales were not significantly associated with HR, PEP, RSA and CAB (p0.07). Conclusion: Results did not support the hypothesis that prenatal maternal psychosocial stress deregulates cardiac AN
Microneedle-Based Transcutaneous Immunisation in Mice with N-Trimethyl Chitosan Adjuvanted Diphtheria Toxoid Formulations
The Role of Teachers' Expectations in the Association between Children's SES and Performance in Kindergarten: A Moderated Mediation Analysis
This study examines the role of teachers' expectations in the association between children's socio-economic background and achievement outcomes. Furthermore, the role of children's ethnicity in moderating this mediated relation is investigated. In the present study, 3,948 children from kindergarten are examined. Data are analysed by means of structural equation modeling. First, results show that teachers' expectations mediate the relation between children's SES and their later language and math achievement, after controlling for children's ethnicity, prior achievement and gender. This result indicates that teachers may exacerbate individual differences between children. Second, children's ethnicity moderates the mediation effect of teachers' expectations with respect to math outcomes. The role of teachers' expectations in mediating the relation between SES and math outcomes is stronger for majority children than for minority children
Intra-tumor heterogeneity in breast cancer has limited impact on transcriptomic-based molecular profiling
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