Cosmology of a Scalar Field Coupled to Matter and an Isotropy-Violating Maxwell Field

Motivated by the couplings of the dilaton in four-dimensional effective actions, we investigate the cosmological consequences of a scalar field coupled both to matter and a Maxwell-type vector field. The vector field has a background isotropy-violating component. New anisotropic scaling solutions which can be responsible for the matter and dark energy dominated epochs are identified and explored. For a large parameter region the universe expands almost isotropically. Using that the CMB quadrupole is extremely sensitive to shear, we constrain the ratio of the matter coupling to the vector coupling to be less than 10^(-5). Moreover, we identify a large parameter region, corresponding to a strong vector coupling regime, yielding exciting and viable cosmologies close to the LCDM limit.Comment: Refs. added, some clarifications. Published in JHEP10(2012)06

Discussing life expectancy with surgical patients: Do patients want to know and how should this information be delivered?

<p>Abstract</p> <p>Background</p> <p>Predicted patient life expectancy (LE) and survival probability (SP), based on a patient's medical history, are important components of surgical decision-making and informed consent. The objective of this study was to assess patients' interpretation of and desire to know information relating to LE, in addition to establishing the most effective format for discussion.</p> <p>Methods</p> <p>A cross sectional survey of 120 patients (mean age = 68.7 years, range 50–90 years), recruited from general urological and surgical outpatient clinics in one District General and one Teaching hospital in Southwest England (UK) was conducted. Patients were included irrespective of their current diagnosis or associated comorbidity. Hypothetical patient case scenarios were used to assess patients' desire to know LE and SP, in addition to their preferred presentation format.</p> <p>Results</p> <p>58% of patients expressed a desire to know their LE and SP, if it were possible to calculate, with 36% not wishing to know either. Patients preferred a combination of numerical and pictorial formats in discussing LE and SP, with numerical, verbal and pictorial formats alone least preferred. 71% patients ranked the survival curve as either their first or second most preferred graph, with 76% rating facial figures their least preferred. No statistically significant difference was noted between sexes or educational backgrounds.</p> <p>Conclusion</p> <p>A proportion of patients seem unwilling to discuss their LE and SP. This may relate to their current diagnosis, level of associated comorbidity or degree of understanding. However it is feasible that by providing this information in a range of presentation formats, greater engagement in the shared decision-making process can be encouraged.</p

Structural Basis for Specificity of Propeptide-Enzyme Interaction in Barley C1A Cysteine Peptidases

C1A cysteine peptidases are synthesized as inactive proenzymes. Activation takes place by proteolysis cleaving off the inhibitory propeptide. The inhibitory capacity of propeptides from barley cathepsin L and B-like peptidases towards commercial and barley cathepsins has been characterized. Differences in selectivity have been found for propeptides from L-cathepsins against their cognate and non cognate enzymes. Besides, the propeptide from barley cathepsin B was not able to inhibit bovine cathepsin B. Modelling of their three-dimensional structures suggests that most propeptide inhibitory properties can be explained from the interaction between the propeptide and the mature cathepsin structures. Their potential use as biotechnological tools is discussed

Clinical trials for stem cell therapies

In recent years, clinical trials with stem cells have taken the emerging field in many new directions. While numerous teams continue to refine and expand the role of bone marrow and cord blood stem cells for their vanguard uses in blood and immune disorders, many others are looking to expand the uses of the various types of stem cells found in bone marrow and cord blood, in particular mesenchymal stem cells, to uses beyond those that could be corrected by replacing cells in their own lineage. Early results from these trials have produced mixed results often showing minor or transitory improvements that may be attributed to extracellular factors. More research teams are accelerating the use of other types of adult stem cells, in particular neural stem cells for diseases where beneficial outcome could result from either in-lineage cell replacement or extracellular factors. At the same time, the first three trials using cells derived from pluripotent cells have begun

Prevalence of insulin resistance and its association with metabolic syndrome criteria among Bolivian children and adolescents with obesity

<p>Abstract</p> <p>Background</p> <p>Obesity is a one of the most common nutritional disorder worldwide, clearly associated with the metabolic syndrome, condition with implications for the development of many chronic diseases.</p> <p>In the poorest countries of Latin America, malnourishment is still the most prevalent nutritional problem, but obesity is emerging in alarming rates over the last 10 years without a predictable association with metabolic syndrome.</p> <p>The objective of our study was to determine the association between insulin-resistance and components of the metabolic syndrome in a group of Bolivian obese children and adolescents. The second objective was determining the relation of acanthosis nigricans and insulin-resistance.</p> <p>Methods</p> <p>We studied 61 obese children and adolescents aged between 5 and 18 years old. All children underwent an oral glucose tolerance test and fasting blood sample was also obtained to measure insulin, HDL, LDL and triglycerides serum level. The diagnosis of metabolic syndrome was defined according to National Cholesterol Education Program-Adult Treatment Panel (NCEP-ATP III) criteria adapted for children.</p> <p>Results</p> <p>Metabolic syndrome was found in 36% of the children, with a higher rate among males (40%) than females (32.2%) (p = 0.599). The prevalence of each of the components was 8.2% in impaired glucose tolerance, 42.6% for high triglyceride level, 55.7% for low levels of high-density lipoprotein cholesterol, and 24.5% for high blood pressure. Insulin resistance (HOMA-IR > 3.5) was found in 39.4% of the children, with a higher rate in males (50%) than females (29%). A strong correlation was found between insulin resistance and high blood pressure (p = 0.0148) and high triglycerides (p = 0.002). No statistical significance was found between the presence of acanthosis nigricans and insulin resistance.</p> <p>Conclusion</p> <p>Metabolic syndrome has a prevalence of 36% in children and adolescent population in the study. Insulin resistance was very common among children with obesity with a significant association with high blood pressure and high triglycerides presence.</p

Bi-galileon theory II: phenomenology

We continue to introduce bi-galileon theory, the generalisation of the single galileon model introduced by Nicolis et al. The theory contains two coupled scalar fields and is described by a Lagrangian that is invariant under Galilean shifts in those fields. This paper is the second of two, and focuses on the phenomenology of the theory. We are particularly interesting in models that admit solutions that are asymptotically self accelerating or asymptotically self tuning. In contrast to the single galileon theories, we find examples of self accelerating models that are simultaneously free from ghosts, tachyons and tadpoles, able to pass solar system constraints through Vainshtein screening, and do not suffer from problems with superluminality, Cerenkov emission or strong coupling. We also find self tuning models and discuss how Weinberg's no go theorem is evaded by breaking Poincar\'e invariance in the scalar sector. Whereas the galileon description is valid all the way down to solar system scales for the self-accelerating models, unfortunately the same cannot be said for self tuning models owing to the scalars backreacting strongly on to the geometry

Site-directed mutations in the C-terminal extension of human aB-Crystalline affect chaperone function and block amyloid fibril formation

Copyright: 2007 Treweek et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background. Alzheimer’s, Parkinson’s and Creutzfeldt-Jakob disease are associated with inappropriate protein deposition and ordered amyloid fibril assembly. Molecular chaperones, including aB-crystallin, play a role in the prevention of protein deposition. Methodology/Principal Findings. A series of site-directed mutants of the human molecular chaperone, aBcrystallin, were constructed which focused on the flexible C-terminal extension of the protein. We investigated the structural role of this region as well as its role in the chaperone function of aB-crystallin under different types of protein aggregation, i.e. disordered amorphous aggregation and ordered amyloid fibril assembly. It was found that mutation of lysine and glutamic acid residues in the C-terminal extension of aB-crystallin resulted in proteins that had improved chaperone activity against amyloid fibril forming target proteins compared to the wild-type protein. Conclusions/Significance. Together, our results highlight the important role of the C-terminal region of aB-crystallin in regulating its secondary, tertiary and quaternary structure and conferring thermostability to the protein. The capacity to genetically modify aB-crystallin for improved ability to block amyloid fibril formation provides a platform for the future use of such engineered molecules in treatment of diseases caused by amyloid fibril formation

An Analysis of Enzyme Kinetics Data for Mitochondrial DNA Strand Termination by Nucleoside Reverse Transcription Inhibitors

Nucleoside analogs used in antiretroviral treatment have been associated with mitochondrial toxicity. The polymerase-γ hypothesis states that this toxicity stems from the analogs' inhibition of the mitochondrial DNA polymerase (polymerase-γ) leading to mitochondrial DNA (mtDNA) depletion. We have constructed a computational model of the interaction of polymerase-γ with activated nucleoside and nucleotide analog drugs, based on experimentally measured reaction rates and base excision rates, together with the mtDNA genome size, the human mtDNA sequence, and mitochondrial dNTP concentrations. The model predicts an approximately 1000-fold difference in the activated drug concentration required for a 50% probability of mtDNA strand termination between the activated di-deoxy analogs d4T, ddC, and ddI (activated to ddA) and the activated forms of the analogs 3TC, TDF, AZT, FTC, and ABC. These predictions are supported by experimental and clinical data showing significantly greater mtDNA depletion in cell culture and patient samples caused by the di-deoxy analog drugs. For zidovudine (AZT) we calculated a very low mtDNA replication termination probability, in contrast to its reported mitochondrial toxicity in vitro and clinically. Therefore AZT mitochondrial toxicity is likely due to a mechanism that does not involve strand termination of mtDNA replication

Prevention of depression and anxiety in later life: design of a randomized controlled trial for the clinical and economic evaluation of a life-review intervention

Abstract Background Depressive and anxiety symptoms in older adults could develop into significant health problems with detrimental effects on quality of life and a possibly poor prognosis. Therefore, there is a need for preventive interventions which are at once effective, acceptable and economic affordable. Methods and design This paper describes the design of a study evaluating "The stories we live by", a preventive life-review group intervention, which was recently developed for adults of 55 years and over with depressive and anxiety symptoms. Both clinical and economic effectiveness will be evaluated in a pragmatic randomized controlled trial. The participants in the intervention condition will receive the 8-session preventive intervention. The participants in the control condition will have access to usual care. Clinical end-terms are depressive and anxiety symptoms, current major depressive episode, quality of life and positive mental health post-treatment (3 months after baseline) and at follow-ups (6 and 12 months after baseline). Additional goals of this study are to identify groups for whom the intervention is particularly effective and to identify the therapeutic pathways that are vital in inducing clinical change. This will be done by analyzing if treatment response is moderated by demographics, personality, past major depressive episodes, important life events and chronically disease, and mediated by reminiscence functions, perceived control, automatic positive thoughts and meaning in life. Finally the cost-effectiveness of the intervention relative to care as usual will be assessed by computing incremental costs per case of depression and anxiety avoided (cost-effectiveness) and per quality adjusted life year (QALY) (cost utility). Discussion It is expected that both the life-review intervention and its evaluation will contribute to the existing body of knowledge in several ways. First, the intervention is unique in linking life-review with narrative therapy and in its focus on specific, positive memories. Second, the evaluation is likely to answer questions regarding the acceptability and cost-effectiveness of life-review that have not been addressed thoroughly until now. Positive results of this study will make available a new evidence-based intervention to improve public health among people of 55 years and over

Gene Expression in a Drosophila Model of Mitochondrial Disease

Background A point mutation in the Drosophila gene technical knockout (tko), encoding mitoribosomal protein S12, was previously shown to cause a phenotype of respiratory chain deficiency, developmental delay, and neurological abnormalities similar to those presented in many human mitochondrial disorders, as well as defective courtship behavior. Methodology/Principal Findings Here, we describe a transcriptome-wide analysis of gene expression in tko25t mutant flies that revealed systematic and compensatory changes in the expression of genes connected with metabolism, including up-regulation of lactate dehydrogenase and of many genes involved in the catabolism of fats and proteins, and various anaplerotic pathways. Gut-specific enzymes involved in the primary mobilization of dietary fats and proteins, as well as a number of transport functions, were also strongly up-regulated, consistent with the idea that oxidative phosphorylation OXPHOS dysfunction is perceived physiologically as a starvation for particular biomolecules. In addition, many stress-response genes were induced. Other changes may reflect a signature of developmental delay, notably a down-regulation of genes connected with reproduction, including gametogenesis, as well as courtship behavior in males; logically this represents a programmed response to a mitochondrially generated starvation signal. The underlying signalling pathway, if conserved, could influence many physiological processes in response to nutritional stress, although any such pathway involved remains unidentified. Conclusions/Significance These studies indicate that general and organ-specific metabolism is transformed in response to mitochondrial dysfunction, including digestive and absorptive functions, and give important clues as to how novel therapeutic strategies for mitochondrial disorders might be developed.Public Library of Scienc