Quantization of Midisuperspace Models

We give a comprehensive review of the quantization of midisuperspace models. Though the main focus of the paper is on quantum aspects, we also provide an introduction to several classical points related to the definition of these models. We cover some important issues, in particular, the use of the principle of symmetric criticality as a very useful tool to obtain the required Hamiltonian formulations. Two main types of reductions are discussed: those involving metrics with two Killing vector fields and spherically symmetric models. We also review the more general models obtained by coupling matter fields to these systems. Throughout the paper we give separate discussions for standard quantizations using geometrodynamical variables and those relying on loop quantum gravity inspired methods.Comment: To appear in Living Review in Relativit

High Resolution Spectral Domain Optical Coherence Tomography (SD-OCT) in Multiple Sclerosis: The First Follow Up Study over Two Years

“Non-invasive, faster and less expensive than MRI” and “the eye is a window to the brain” are recent slogans promoting optical coherence tomography (OCT) as a new surrogate marker in multiple sclerosis (MS). Indeed, OCT allows for the first time a non-invasive visualization of axons of the central nervous system (CNS). Reduction of retina nerve fibre layer (RNFL) thickness was suggested to correlate with disease activity and duration. However, several issues are unclear: Do a few million axons, which build up both optic nerves, really resemble billions of CNS neurons? Does global CNS damage really result in global RNFL reduction? And if so, does global RNFL reduction really exist in all MS patients, and follow a slowly but steadily ongoing pattern? How can these (hypothesized) subtle global RNFL changes be reliably measured and separated from the rather gross RNFL changes caused by optic neuritis? Before generally being accepted, this interpretation needs further critical and objective validation.We prospectively studied 37 MS patients with relapsing remitting (n = 27) and secondary progressive (n = 10) course on two occasions with a median interval of 22.4±0.5 months [range 19–27]. We used the high resolution spectral domain (SD-)OCT with the Spectralis 3.5 mm circle scan protocol with locked reference images and eye tracking mode. Patients with an attack of optic neuritis within 12 months prior to the onset of the study were excluded.Although the disease was highly active over the observation period in more than half of the included relapsing remitting MS patients (19 patients/32 relapses) and the initial RNFL pattern showed a broad range, from normal to markedly reduced thickness, no significant changes between baseline and follow-up examinations could be detected.These results show that caution is required when using OCT for monitoring disease activity and global axonal injury in MS

A prospective study of decline in fat free mass and skeletal muscle strength in chronic obstructive pulmonary disease

BACKGROUND: Skeletal muscle depletion is an important complication of chronic obstructive pulmonary disease (COPD) but little prospective data exists about the rate at which it occurs and the factors that promote its development. We therefore prospectively investigated the impact of disease severity, exacerbation frequency and treatment with corticosteroids on change in body composition and maximum isometric quadriceps strength (QMVC) over one year. METHODS: 64 patients with stable COPD (FEV(1 )mean (SD) 35.8(18.4) %predicted) were recruited from clinic and studied on two occasions one year apart. Fat free mass was determined using bioelectrical impedance analysis and a disease specific regression equation. RESULTS: QMVC fell from 34.8(1.5) kg to 33.3(1.5) kg (p = 0.04). The decline in quadriceps strength was greatest in those with the highest strength at baseline (R -0.28 p = 0.02) and was not correlated with lung function, exacerbation frequency or steroid treatment. Decline in fat free mass was similarly higher in those with largest FFM at baseline (R = -0.31 p = 0.01) but was more strongly correlated with greater gas trapping (R = -0.4 p = 0.001). Patients with frequent exacerbations (>1 per year) (n = 36) experienced a greater decline in fat free mass compared to infrequent exacerbators (n = 28) -1.3(3.7)kg vs. +1.2(3.1)kg (p = 0.005), as did patients on maintenance oral steroids (n = 8) -2.8(3.3) kg vs. +0.2(3.5) kg (p = 0.024) whereas in those who stopped smoking (n = 7) fat free mass increased; +2.7(3.1) kg vs. -0.51(3.5) kg (p = 0.026). CONCLUSION: Decline in fat free mass in COPD is associated with worse lung function, continued cigarette consumption and frequent exacerbations. Factors predicting progression of quadriceps weakness could not be identified from the present cohort

Hepatitis B screening in the Turkish-Dutch population in Rotterdam, the Netherlands; qualitative assessment of socio-cultural determinants

Background. Hepatitis B is an important health problem in the Turkish community in the Netherlands. Increased voluntary screening is necessary in this community, to detect individuals eligible for treatment and to prevent further transmission of the disease. Methods. We investigated socio-cultural determinants associated with hepatitis B screening in male and female, first and second generation Turkish migrants, by means of Focus Group Discussions. Results. Socio-cultural themes related to hepatitis B screening were identified; these were social norm, social support, sensitivity regarding sexuality, reputation, responsiveness to authority, religious responsibility, cleanliness and religious doctrine regarding health and disease, and the perceived efficacy of Dutch health care services. Motivating factors were the (religious) responsibility for one's health, the perceived obligation when being invited for screening, and social support to get tested for hepatitis B. Perceived barriers were the association of hepatitis B screening with STDs or sexual activity, the perception of low control over one's health, and the perceived low efficacy of the Dutch health care services. Reputation could act as either a motivator or barrier. Conclusion. This study identified relevant socio-cultural themes related to hepatitis B screening, which may serve to customize interventions aimed at the promotion of voluntary hepatitis B screening in the Turkish-Dutch population in the Netherlands

The unfolded protein response and its relevance to connective tissue diseases

The unfolded protein response (UPR) has evolved to counter the stresses that occur in the endoplasmic reticulum (ER) as a result of misfolded proteins. This sophisticated quality control system attempts to restore homeostasis through the action of a number of different pathways that are coordinated in the first instance by the ER stress-senor proteins IRE1, ATF6 and PERK. However, prolonged ER-stress-related UPR can have detrimental effects on cell function and, in the longer term, may induce apoptosis. Connective tissue cells such as fibroblasts, osteoblasts and chondrocytes synthesise and secrete large quantities of proteins and mutations in many of these gene products give rise to heritable disorders of connective tissues. Until recently, these mutant gene products were thought to exert their effect through the assembly of a defective extracellular matrix that ultimately disrupted tissue structure and function. However, it is now becoming clear that ER stress and UPR, because of the expression of a mutant gene product, is not only a feature of, but may be a key mediator in the initiation and progression of a whole range of different connective tissue diseases. This review focuses on ER stress and the UPR that characterises an increasing number of connective tissue diseases and highlights novel therapeutic opportunities that may arise

Exploration of Shared Genetic Architecture Between Subcortical Brain Volumes and Anorexia Nervosa

In MRI scans of patients with anorexia nervosa (AN), reductions in brain volume are often apparent. However, it is unknown whether such brain abnormalities are influenced by genetic determinants that partially overlap with those underlying AN. Here, we used a battery of methods (LD score regression, genetic risk scores, sign test, SNP effect concordance analysis, and Mendelian randomization) to investigate the genetic covariation between subcortical brain volumes and risk for AN based on summary measures retrieved from genome-wide association studies of regional brain volumes (ENIGMA consortium, n = 13,170) and genetic risk for AN (PGC-ED consortium, n = 14,477). Genetic correlations ranged from − 0.10 to 0.23 (all p > 0.05). There were some signs of an inverse concordance between greater thalamus volume and risk for AN (permuted p = 0.009, 95% CI: [0.005, 0.017]). A genetic variant in the vicinity of ZW10, a gene involved in cell division, and neurotransmitter and immune system relevant genes, in particular DRD2, was significantly associated with AN only after conditioning on its association with caudate volume (pFDR = 0.025). Another genetic variant linked to LRRC4C, important in axonal and synaptic development, reached significance after conditioning on hippocampal volume (pFDR = 0.021). In this comprehensive set of analyses and based on the largest available sample sizes to date, there was weak evidence for associations between risk for AN and risk for abnormal subcortical brain volumes at a global level (that is, common variant genetic architecture), but suggestive evidence for effects of single genetic markers. Highly powered multimodal brain- and disorder-related genome-wide studies are needed to further dissect the shared genetic influences on brain structure and risk for AN