Detecting the orientation of magnetic fields in galaxy clusters

Clusters of galaxies, filled with hot magnetized plasma, are the largest bound objects in existence and an important touchstone in understanding the formation of structures in our Universe. In such clusters, thermal conduction follows field lines, so magnetic fields strongly shape the cluster's thermal history; that some have not since cooled and collapsed is a mystery. In a seemingly unrelated puzzle, recent observations of Virgo cluster spiral galaxies imply ridges of strong, coherent magnetic fields offset from their centre. Here we demonstrate, using three-dimensional magnetohydrodynamical simulations, that such ridges are easily explained by galaxies sweeping up field lines as they orbit inside the cluster. This magnetic drape is then lit up with cosmic rays from the galaxies' stars, generating coherent polarized emission at the galaxies' leading edges. This immediately presents a technique for probing local orientations and characteristic length scales of cluster magnetic fields. The first application of this technique, mapping the field of the Virgo cluster, gives a startling result: outside a central region, the magnetic field is preferentially oriented radially as predicted by the magnetothermal instability. Our results strongly suggest a mechanism for maintaining some clusters in a 'non-cooling-core' state.Comment: 48 pages, 21 figures, revised version to match published article in Nature Physics, high-resolution version available at http://www.cita.utoronto.ca/~pfrommer/Publications/pfrommer-dursi.pd

Relations Among Anhedonia, Reinforcement Learning, and Global Functioning in Help-seeking Youth

Dysfunction in the neural circuits underlying salience signaling is implicated in symptoms of psychosis and may predict conversion to a psychotic disorder in youth at clinical high risk (CHR) for psychosis. Additionally, negative symptom severity, including consummatory and anticipatory aspects of anhedonia, may predict functional outcome in individuals with schizophrenia-spectrum disorders. However, it is unclear whether anhedonia is related to the ability to attribute incentive salience to stimuli (through reinforcement learning [RL]) and whether measures of anhedonia and RL predict functional outcome in a younger, help-seeking population. We administered the Salience Attribution Test (SAT) to 33 participants who met criteria for either CHR or a recent-onset psychotic disorder and 29 help-seeking youth with nonpsychotic disorders. In the SAT, participants must identify relevant and irrelevant stimulus dimensions and be sensitive to different reinforcement probabilities for the 2 levels of the relevant dimension ("adaptive salience"). Adaptive salience attribution was positively related to both consummatory pleasure and functioning in the full sample. Analyses also revealed an indirect effect of adaptive salience on the relation between consummatory pleasure and both role (αβ = .22, 95% CI = 0.02, 0.48) and social functioning (αβ = .14, 95% CI = 0.02, 0.30). These findings suggest a distinct pathway to poor global functioning in help-seeking youth, via impaired reward sensitivity and RL

The cost-effectiveness of early noninvasive ventilation for ALS patients

BACKGROUND: Optimal timing of noninvasive positive pressure ventilation (NIPPV) initiation in patients with amyotrophic lateral sclerosis (ALS) is unknown, but NIPPV appears to benefit ALS patients who are symptomatic from pulmonary insufficiency. This has prompted research proposals of earlier NIPPV initiation in the ALS disease course in an attempt to further improve ALS patient quality of life and perhaps survival. We therefore used a cost-utility analysis to determine a priori what magnitude of health-related quality of life (HRQL) improvement early NIPPV initiation would need to achieve to be cost-effective in a future clinical trial. METHODS: Using a Markov decision analytic model we calculated the benefit in health-state utility that NIPPV initiated at ALS diagnosis must achieve to be cost-effective. The primary outcome was the percent utility gained through NIPPV in relation to two common willingness-to-pay thresholds: $50,000 and$100,000 per quality-adjusted life year (QALY). RESULTS: Our results indicate that if NIPPV begun at the time of diagnosis improves ALS patient HRQL as little as 13.5%, it would be a cost-effective treatment. Tolerance of NIPPV (assuming a 20% improvement in HRQL) would only need to exceed 18% in our model for treatment to remain cost-effective using a conservative willingness-to-pay threshold of $50,000 per QALY. CONCLUSION: If early use of NIPPV in ALS patients is shown to improve HRQL in future studies, it is likely to be a cost-effective treatment. Clinical trials of NIPPV begun at the time of ALS diagnosis are therefore warranted from a cost-effectiveness standpoint

The effects of the Islamic revolution and the gulf war on Iran's economy

The Islamic revolution, followed by the eight-year Gulf war, has caused severe disruption and extensive changes in the structure of the Iranian economy. This thesis is concerned with an analytical study of Iran’s economy In the period from the Shah's western-style modernisation to the Islamic revolution and the war with Iraq. Thus, the thesis provides first, an overview of the economic development and industrialisation activity under the Shah, which glides a yardstick for understanding the post-revolutionary economy. Secondly, the thesis examines the concept of Islamic economics as articulated by the prominent contemporary Shi'i figures that continue to influence the post-revolutionary economic policies. Thirdly, the major part of the thesis devotes considerable attention to the study and evaluation of the post-revolutionary economy, focusing on agriculture, industry, foreign and domestic trade. Islamic balancing, public finance, the oil sector and the oil war. The latter was a determining factor in the continuation of the Gulf war. The appraisal and the overall picture of the post-revolutionary economy makes bleak reading. The negative Impact of the revolution and the war has left Iran with a shattered infrastructure and a moribund industrial base. Unprecedented destruction of wealth, both in human and non-human terms, has further exacerbated the pre-revolutionary economic problems. The politico-religious government has not been able to address the country's economic Ills effectively, partly owing to self -imposed constraints. A lack of active and structured economic policies has adversely affected all sectors of the economy, in particular, agriculture. While facing the daunting task of post-war reconstruction, Iran, more than ever before, is dependent on trading oil in exchange for basic commodities and consumer goods

A four-helix bundle stores copper for methane oxidation

Methane-oxidising bacteria (methanotrophs) require large quantities of copper for the membrane-bound (particulate) methane monooxygenase (pMMO). Certain methanotrophs are also able to switch to using the iron-containing soluble MMO (sMMO) to catalyse methane oxidation, with this switchover regulated by copper. MMOs are Nature’s primary biological mechanism for suppressing atmospheric levels of methane, a potent greenhouse gas. Furthermore, methanotrophs and MMOs have enormous potential in bioremediation and for biotransformations producing bulk and fine chemicals, and in bioenergy, particularly considering increased methane availability from renewable sources and hydraulic fracturing of shale rock. We have discovered and characterised a novel copper storage protein (Csp1) from the methanotroph Methylosinus trichosporium OB3b that is exported from the cytosol, and stores copper for pMMO. Csp1 is a tetramer of 4-helix bundles with each monomer binding up to 13 Cu(I) ions in a previously unseen manner via mainly Cys residues that point into the core of the bundle. Csp1 is the first example of a protein that stores a metal within an established protein-folding motif. This work provides a detailed insight into how methanotrophs accumulate copper for the oxidation of methane. Understanding this process is essential if the wide-ranging biotechnological applications of methanotrophs are to be realised. Cytosolic homologues of Csp1 are present in diverse bacteria thus challenging the dogma that such organisms do not use copper in this location

The value of including boys in an HPV vaccination programme: a cost-effectiveness analysis in a low-resource setting

We assessed the cost-effectiveness of including boys vs girls alone in a pre-adolescent vaccination programme against human papillomavirus (HPV) types 16 and 18 in Brazil. Using demographic, epidemiological, and cancer data from Brazil, we developed a dynamic transmission model of HPV infection between males and females. Model-projected reductions in HPV incidence under different vaccination scenarios were applied to a stochastic model of cervical carcinogenesis to project lifetime costs and benefits. We assumed vaccination prevented HPV-16 and -18 infections in individuals not previously infected, and protection was lifelong. Coverage was varied from 0-90% in both genders, and cost per-vaccinated individual was varied from I$25 to 400. At 90$50, vaccinating girls alone was <$200 per year of life saved (YLS), while including boys ranged from$810–18 650 per YLS depending on coverage. For all coverage levels, increasing coverage in girls was more effective and less costly than including boys in the vaccination programme. In a resource-constrained setting such as Brazil, our results support that the first priority in reducing cervical cancer mortality should be to vaccinate pre-adolescent girls

Clinical Subtypes of Depression Are Associated with Specific Metabolic Parameters and Circadian Endocrine Profiles in Women: The Power Study

Major depressive disorder (MDD) has been associated with adverse medical consequences, including cardiovascular disease and osteoporosis. Patients with MDD may be classified as having melancholic, atypical, or undifferentiated features. The goal of the present study was to assess whether these clinical subtypes of depression have different endocrine and metabolic features and consequently, varying medical outcomes.Premenopausal women, ages 21 to 45 years, with MDD (N = 89) and healthy controls (N = 44) were recruited for a prospective study of bone turnover. Women with MDD were classified as having melancholic (N = 51), atypical (N = 16), or undifferentiated (N = 22) features. Outcome measures included: metabolic parameters, body composition, bone mineral density (BMD), and 24 hourly sampling of plasma adrenocorticotropin (ACTH), cortisol, and leptin.Compared with control subjects, women with undifferentiated and atypical features of MDD exhibited greater BMI, waist/hip ratio, and whole body and abdominal fat mass. Women with undifferentiated MDD characteristics also had higher lipid and fasting glucose levels in addition to a greater prevalence of low BMD at the femoral neck compared to controls. Elevated ACTH levels were demonstrated in women with atypical features of depression, whereas higher mean 24-hour leptin levels were observed in the melancholic subgroup.Pre-menopausal women with various features of MDD exhibit metabolic, endocrine, and BMD features that may be associated with different health consequences.ClinicalTrials.gov NCT00006180

Composite structural motifs of binding sites for delineating biological functions of proteins

Most biological processes are described as a series of interactions between proteins and other molecules, and interactions are in turn described in terms of atomic structures. To annotate protein functions as sets of interaction states at atomic resolution, and thereby to better understand the relation between protein interactions and biological functions, we conducted exhaustive all-against-all atomic structure comparisons of all known binding sites for ligands including small molecules, proteins and nucleic acids, and identified recurring elementary motifs. By integrating the elementary motifs associated with each subunit, we defined composite motifs which represent context-dependent combinations of elementary motifs. It is demonstrated that function similarity can be better inferred from composite motif similarity compared to the similarity of protein sequences or of individual binding sites. By integrating the composite motifs associated with each protein function, we define meta-composite motifs each of which is regarded as a time-independent diagrammatic representation of a biological process. It is shown that meta-composite motifs provide richer annotations of biological processes than sequence clusters. The present results serve as a basis for bridging atomic structures to higher-order biological phenomena by classification and integration of binding site structures.Comment: 34 pages, 7 figure

A systematic review of frameworks for the interrelationships of mental health evidence and policy in low- and middle-income countries

Background: The interrelationships between research evidence and policy-making are complex. Different theoretical frameworks exist to explain general evidence–policy interactions. One largely unexplored element of these interrelationships is how evidence interrelates with, and influences, policy/political agenda-setting. This review aims to identify the elements and processes of theories, frameworks and models on interrelationships of research evidence and health policy-making, with a focus on actionability and agenda-setting in the context of mental health in low- and middle-income countries (LMICs). Methods: A systematic review of theories was conducted based on the BeHeMOTh search method, using a tested and refined search strategy. Nine electronic databases and other relevant sources were searched for peer-reviewed and grey literature. Two reviewers screened the abstracts, reviewed full-text articles, extracted data and performed quality assessments. Analysis was based on a thematic analysis. The included papers had to present an actionable theoretical framework/model on evidence and policy interrelationships, such as knowledge translation or evidence-based policy, specifically target the agenda-setting process, focus on mental health, be from LMICs and published in English. Results: From 236 publications included in the full text analysis, no studies fully complied with our inclusion criteria. Widening the focus by leaving out ‘agenda-setting’, we included ten studies, four of which had unique conceptual frameworks focusing on mental health and LMICs but not agenda-setting. The four analysed frameworks confirmed research gaps from LMICs and mental health, and a lack of focus on agenda-setting. Frameworks and models from other health and policy areas provide interesting conceptual approaches and lessons with regards to agenda-setting. Conclusion: Our systematic review identified frameworks on evidence and policy interrelations that differ in their elements and processes. No framework fulfilled all inclusion criteria. Four actionable frameworks are applicable to mental health and LMICs, but none specifically target agenda-setting. We have identified agenda-setting as a research theory gap in the context of mental health knowledge translation in LMICs. Frameworks from other health/policy areas could offer lessons on agenda-setting and new approaches for creating policy impact for mental health and to tackle the translational gap in LMICs

MycoRRdb: A Database of Computationally Identified Regulatory Regions within Intergenic Sequences in Mycobacterial Genomes

The identification of regulatory regions for a gene is an important step towards deciphering the gene regulation. Regulatory regions tend to be conserved under evolution that facilitates the application of comparative genomics to identify such regions. The present study is an attempt to make use of this attribute to identify regulatory regions in the Mycobacterium species followed by the development of a database, MycoRRdb. It consist the regulatory regions identified within the intergenic distances of 25 mycobacterial species. MycoRRdb allows to retrieve the identified intergenic regulatory elements in the mycobacterial genomes. In addition to the predicted motifs, it also allows user to retrieve the Reciprocal Best BLAST Hits across the mycobacterial genomes. It is a useful resource to understand the transcriptional regulatory mechanism of mycobacterial species. This database is first of its kind which specifically addresses cis-regulatory regions and also comprehensive to the mycobacterial species. Database URL: http://mycorrdb.uohbif.in