Mach's Principle and Model for a Broken Symmetric Theory of Gravity

We investigate spontaneous symmetry breaking in a conformally invariant gravitational model. In particular, we use a conformally invariant scalar tensor theory as the vacuum sector of a gravitational model to examine the idea that gravitational coupling may be the result of a spontaneous symmetry breaking. In this model matter is taken to be coupled with a metric which is different but conformally related to the metric appearing explicitly in the vacuum sector. We show that after the spontaneous symmetry breaking the resulting theory is consistent with Mach's principle in the sense that inertial masses of particles have variable configurations in a cosmological context. Moreover, our analysis allows to construct a mechanism in which the resulting large vacuum energy density relaxes during evolution of the universe.Comment: 9 pages, no figure

Lifestyle, Inflammation, and Vascular Calcification in Kidney Transplant Recipients:Perspectives on Long-Term Outcomes

After decades of pioneering and improvement, kidney transplantation is now the renal replacement therapy of choice for most patients with end-stage kidney disease (ESKD). Where focus has traditionally been on surgical techniques and immunosuppressive treatment with prevention of rejection and infection in relation to short-term outcomes, nowadays, so many people are long-living with a transplanted kidney that lifestyle, including diet and exposure to toxic contaminants, also becomes of importance for the kidney transplantation field. Beyond hazards of immunological nature, a systematic assessment of potentially modifiable-yet rather overlooked-risk factors for late graft failure and excess cardiovascular risk may reveal novel targets for clinical intervention to optimize long-term health and downturn current rates of premature death of kidney transplant recipients (KTR). It should also be realized that while kidney transplantation aims to restore kidney function, it incompletely mitigates mechanisms of disease such as chronic low-grade inflammation with persistent redox imbalance and deregulated mineral and bone metabolism. While the vicious circle between inflammation and oxidative stress as common final pathway of a multitude of insults plays an established pathological role in native chronic kidney disease, its characterization post-kidney transplant remains less than satisfactory. Next to chronic inflammatory status, markedly accelerated vascular calcification persists after kidney transplantation and is likewise suggested a major independent mechanism, whose mitigation may counterbalance the excess risk of cardiovascular disease post-kidney transplant. Hereby, we first discuss modifiable dietary elements and toxic environmental contaminants that may explain increased risk of cardiovascular mortality and late graft failure in KTR. Next, we specify laboratory and clinical readouts, with a postulated role within persisting mechanisms of disease post-kidney transplantation (i.e., inflammation and redox imbalance and vascular calcification), as potential non-traditional risk factors for adverse long-term outcomes in KTR. Reflection on these current research opportunities is warranted among the research and clinical kidney transplantation community

Pharmacological Rationale for Targeting IL-17 in Asthma

Asthma is a respiratory disease that currently affects around 300 million people worldwide and is defined by coughing, shortness of breath, wheezing, mucus overproduction, chest tightness, and expiratory airflow limitation. Increased levels of interleukin 17 (IL-17) have been observed in sputum, nasal and bronchial biopsies, and serum of patients with asthma compared to healthy controls. Patients with higher levels of IL-17 have a more severe asthma phenotype. Biologics are available for T helper 2 (Th2)-high asthmatics, but the Th17-high subpopulation has a relatively low response to these treatments, rendering it a rather severe asthma phenotype to treat. Several experimental models suggest that targeting the IL-17 pathway may be beneficial in asthma. Moreover, as increased activation of the Th17/IL-17 axis is correlated with reduced inhaled corticosteroids (ICS) sensitivity, targeting the IL-17 pathway might reverse ICS unresponsiveness. In this review, we present and discuss the current knowledge on the role of IL-17 in asthma and its interaction with the Th2 pathway, focusing on the rationale for therapeutic targeting of the IL-17 pathway

The relationship between anti-mullerian hormone in women receiving fertility assessments and age at menopause in subfertile women: evidence from large population studies

<p>Context: Anti-Müllerian hormone (AMH) concentration reflects ovarian aging and is argued to be a useful predictor of age at menopause (AMP). It is hypothesized that AMH falling below a critical threshold corresponds to follicle depletion, which results in menopause. With this threshold, theoretical predictions of AMP can be made. Comparisons of such predictions with observed AMP from population studies support the role for AMH as a forecaster of menopause.</p> <p>Objective: The objective of the study was to investigate whether previous relationships between AMH and AMP are valid using a much larger data set.</p> <p>Setting: AMH was measured in 27 563 women attending fertility clinics.</p> <p>Study Design: From these data a model of age-related AMH change was constructed using a robust regression analysis. Data on AMP from subfertile women were obtained from the population-based Prospect-European Prospective Investigation into Cancer and Nutrition (Prospect-EPIC) cohort (n = 2249). By constructing a probability distribution of age at which AMH falls below a critical threshold and fitting this to Prospect-EPIC menopausal age data using maximum likelihood, such a threshold was estimated.</p> <p>Main Outcome: The main outcome was conformity between observed and predicted AMP.</p> <p>Results: To get a distribution of AMH-predicted AMP that fit the Prospect-EPIC data, we found the critical AMH threshold should vary among women in such a way that women with low age-specific AMH would have lower thresholds, whereas women with high age-specific AMH would have higher thresholds (mean 0.075 ng/mL; interquartile range 0.038–0.15 ng/mL). Such a varying AMH threshold for menopause is a novel and biologically plausible finding. AMH became undetectable (<0.2 ng/mL) approximately 5 years before the occurrence of menopause, in line with a previous report.</p> <p>Conclusions: The conformity of the observed and predicted distributions of AMP supports the hypothesis that declining population averages of AMH are associated with menopause, making AMH an excellent candidate biomarker for AMP prediction. Further research will help establish the accuracy of AMH levels to predict AMP within individuals.</p&gt

Mediators of the effect of the JUMP-in intervention on physical activity and sedentary behavior in Dutch primary schoolchildren from disadvantaged neighborhoods.

<p>Abstract</p> <p>Background</p> <p>Important health benefits can be achieved when physical activity in children from low socio-economic status is promoted and sedentariness is limited. By specifying the mediating mechanisms of existing interventions one can improve future physical activity interventions. This study explored potential mediators of the long-term effect of the school-based multicomponent JUMP-in intervention on sport participation, outdoor play and screen time in Dutch primary schoolchildren from disadvantaged neighborhoods.</p> <p>Methods</p> <p>In total, 600 primary schoolchildren (aged 9.8 ± 0.7, 51% girls, 13% Dutch ethnicity, 35% overweight) from 9 intervention and 10 control schools were included in the analyses. JUMP-in was developed using Intervention Mapping, and targeted psychological and environmental determinants of physical activity. Outcome behaviors were self-reported sport participation, outdoor play, TV-viewing behavior and computer use. Potential mediators were self-reported psychological, social and physical environmental factors.</p> <p>Results</p> <p>JUMP-in was effective in improving sport participation after 20 months, but not in improving outdoor play, or reducing TV-viewing or computer time. JUMP-in was not effective in changing hypothesized mediators so no significant mediated effects could be identified. However, changes in self-efficacy, social support and habit strength were positively associated with changes in sport participation, and changes in social support, self-efficacy, perceived planning skills, enjoyment and habit strength were positively associated with changes in outdoor play. Changes in enjoyment was positively associated with changes in TV-viewing while parental rules were negatively associated. Having a computer in the bedroom and enjoyment were positively associated with changes in computer use, while changes in parental rules were negatively associated.</p> <p>Conclusions</p> <p>Besides a significant positive effect on sports participation, no significant intervention effect on outdoor play, screen time or any of the potential mediators was found. This suggest that other (unmeasured) factors operated as mediating mechanisms of the intervention, that we used unsuccessful intervention strategies, that the strategies were inappropriately implemented, or that children are unable to accurately recall past activities and cognitions. Additionally, the school setting might not be the sole channel to influence leisure time activities. Still, several personal and environmental constructs were found to be relevant in predicting change in sport participation, outdoor play and screen behavior and seem to be potential mediators. Future interventions are recommended including more effective strategies targeting these relevant constructs, addressing different constructs (e.g. pedagogic skills of parents), and focusing on different implementation settings.</p> <p>Trail registration</p> <p>ISRCTN17489378</p