Hamiltonian path analysis of viral genomes

Cryo-electron microscopy (EM) is undergoing a revolution, enabling the study of viral pathogens in unprecedented detail. The asymmetric EM reconstruction of bacteriophage MS2 at medium resolution (8.7 Å) by Koning et al.1, and the subsequent reconstruction at even higher resolution (3.6 Å) by Dai et al.2 revealed the structures of both the protein shell and the asym- metric genomic RNA and the unique maturation protein (A). It is the start of a wave of such structural data for viruses, and calls for the development of new analytical tools to describe the results. One approach is Hamiltonian path analysis (HPA) that we introduced to describe repeated, sequence-specific contacts between the MS2 genome and its protein shell3. Here, we describe how HPA is consistent with the new structures and, in turn, how it extends our understanding beyond the structural data alone

Simply-supported multi-layered beams for energy harvesting

This paper develops an analytical model for predicting the performance of simply-supported multi-layered piezoelectric vibrating energy harvesters. The model includes the effects of material and geometric nonlinearities, as well as axial pre-tension/compression, and is validated against experimental devices for a large range of base accelerations. Numerical and experimental investigations are performed to understand the benefits of using simply supported devices compared to cantilevered devices. Comparisons are made in an unbiased manner by tuning the resonant frequency to the same value by modifying the geometry, and the results obtained indicate that simply supported devices are capable of generating higher voltage levels than cantilever devices. The model is also used to investigate the benefits of using multi-layered devices to improve power density. Depending on harvester composition, power-per-unit-volume of piezoelectric material for a device is increased through the stacking of layers

Hungary and the European Union: the political implications of societal security promotion

Hungary's constitutional commitment to support kin-nationals beyond its borders (nation policy) has been a central feature of its post-1989 foreign policy and highlights a particularly important national security concern—the societal security of national identity, culture, language and tradition. This article examines Hungary's societal security concerns and the policy methods it utilises, including its EU membership and the promotion of minority rights at the European level, to help combat these concerns. It is suggested that Hungary has found it somewhat difficult to balance its societal security policy objective with internal economic demands on its welfare system and its external foreign policy objective to maintain good neighbourly relations. This article also notes that Hungary's attempts to Europeanise, or rather 'EU-ise', minority and ethnic rights issues as a means to enhance societal security for the Hungarian nation has certain political consequences for the EU. This suggests that societal security provision is an issue that cannot be overlooked when trying to understand the longer-term implications of EU eastern enlargement

Safety and effectiveness of adalimumab in a clinical setting that reflects Canadian standard of care for the treatment of rheumatoid arthritis (RA): Results from the CanACT study

<p>Abstract</p> <p>Background</p> <p>This multicenter, open-label, prospective, single cohort study evaluated the effectiveness and safety of adalimumab in a clinical setting reflecting the Canadian standard of care for the treatment of patients with rheumatoid arthritis (RA).</p> <p>Methods</p> <p>Patients ≥ 18 years of age with a history of active RA ≥ 3 months and fulfilling Canadian requirements for biological therapy received adalimumab 40 mg subcutaneously every other week for 12 weeks. Pre-study DMARD treatment regimens, corticosteroids, or NSAIDs were allowed throughout the study. The primary effectiveness outcome measure was the mean change in 28-joint disease activity score (DAS28) from baseline to Week 12. Secondary measures included the proportion of patients achieving joint remission (DAS28 < 2.6) and low-disease activity (DAS28 < 3.2) at Week 12, and European League Against Rheumatism (EULAR: moderate and good) and American College of Rheumatology (ACR: ACR20, 50, and 70) responses, as well as responses in ACR core components at Weeks 4, 8, and 12. Subgroup analysis included a comparison of patients naïve to biological DMARD (BDMARD) therapy versus BDMARD-experienced patients. Safety was assessed in terms of adverse and serious adverse events.</p> <p>Results</p> <p>A total of 879 patients (mean disease duration > 12 years) were enrolled; 772 (87.9%) completed the 12-week period. Adalimumab treatment was associated with rapid and sustained improvements in the signs and symptoms of RA. Significant improvements in mean DAS28 score were observed as early as Week 4. After 12 weeks of adalimumab treatment, 15.3% and 28.9% of patients achieved clinical remission and low-disease activity, respectively. Similarly, significant improvements in ACR core components were observed as early as Week 4, with continued improvements occurring through 12 weeks. Patients naïve to BDMARD therapy demonstrated numerically greater clinical responses when compared with patients who had experienced prior BDMARD therapy, although both subgroups were associated with significant improvements from baseline. The rates and types of adverse events, as well as the results of laboratory measures, demonstrated that adalimumab was generally safe and well-tolerated.</p> <p>Conclusions</p> <p>This study demonstrated that, under conditions reflective of the normal clinical practice in Canada, adalimumab is an effective and safe treatment for patients with RA.</p> <p>Trial registration</p> <p><a href="http://www.clinicaltrials.gov/ct2/show/NCT00649545">NCT00649545</a>.</p

The clinical features of the piriformis syndrome: a systematic review

Piriformis syndrome, sciatica caused by compression of the sciatic nerve by the piriformis muscle, has been described for over 70 years; yet, it remains controversial. The literature consists mainly of case series and narrative reviews. The objectives of the study were: first, to make the best use of existing evidence to estimate the frequencies of clinical features in patients reported to have PS; second, to identify future research questions. A systematic review was conducted of any study type that reported extractable data relevant to diagnosis. The search included all studies up to 1 March 2008 in four databases: AMED, CINAHL, Embase and Medline. Screening, data extraction and analysis were all performed independently by two reviewers. A total of 55 studies were included: 51 individual and 3 aggregated data studies, and 1 combined study. The most common features found were: buttock pain, external tenderness over the greater sciatic notch, aggravation of the pain through sitting and augmentation of the pain with manoeuvres that increase piriformis muscle tension. Future research could start with comparing the frequencies of these features in sciatica patients with and without disc herniation or spinal stenosis

Combined resistance and aerobic exercise intervention improves fitness, insulin resistance and quality of life in survivors of childhood haemopoietic stem cell transplantation with total body irradiation

Purpose: To investigate the effects of a supervised combined resistance and aerobic training programme on cardiorespiratory fitness, body composition, insulin resistance and quality of life (QoL) in survivors of childhood haematopoietic stem cell transplantation (HSCT) with total body irradiation (TBI). Participants: HSCT/TBI survivors (n = 20; 8 females). Mean (range) for age at study and time since HSCT/TBI was 16.7 (10.9‐24.5) and 8.4 (2.3‐16.0) years, respectively. Methods: After a 6‐month run‐in, participants undertook supervised 45‐ to 60‐minute resistance and aerobic training twice weekly for 6 months, with a 6‐month follow‐up. The following assessments were made at 0, 6 (start of exercise programme), 12 (end of exercise programme) and 18 months: Body composition via dual energy X‐ray absorptiometry, homeostatic model assessment of insulin resistance (HOMA‐IR), cardiorespiratory fitness (treadmill‐based peak rate of oxygen uptake (VO2 peak) test), QoL questionnaires (36‐Item Short Form Health Survey (SF‐36) and Minneapolis‐Manchester Quality of Life Instrument (MMQL). Results: Results expressed as mean (standard deviation) or geometric mean (range). There were significant improvements in VO2 peak (35.7 (8.9) vs 41.7 (16.1) mL/min/kg, P = 0.05), fasted plasma insulin (16.56 (1.48‐72.8) vs 12.62 (1.04‐54.97) mIU/L, P = 0.03) and HOMA‐IR (3.65 (0.30‐17.26) vs 2.72 (0.22‐12.89), P = 0.02) after the exercise intervention. There were also significant improvements in the SF‐36 QoL general health domain (69.7 (14.3) vs 72.7 (16.0), P = 0.001) and the MMQL school domain (69.1 (25.2) vs (79.3 (21.6), P = 0.03) during the exercise intervention. No significant changes were observed in percentage body fat, fat mass or lean mass. Conclusion: The supervised 6‐month combined resistance and aerobic exercise programme significantly improved cardiorespiratory fitness, insulin resistance and QoL in childhood HSCT/TBI survivors, with no change in body composition, suggesting a metabolic training effect on muscle. These data support a role for targeted physical rehabilitation services in this group at high risk of diabetes and cardiovascular disease

Cleavage of ST6Gal I by Radiation-Induced BACE1 Inhibits Golgi-Anchored ST6Gal I-Mediated Sialylation of Integrin β1 and Migration in Colon Cancer Cells

<p>Abstract</p> <p>Background</p> <p>Previously, we found that β-galactoside α2,6-sialyltransferase (ST6Gal I), an enzyme that adds sialic acids to N-linked oligosaccharides of glycoproteins and is frequently overexpressed in cancer cells, is up-regulated by ionizing radiation (IR) and cleaved to a form possessing catalytic activity comparable to that of the Golgi-localized enzyme. Moreover, this soluble form is secreted into the culture media. Induction of ST6Gal I significantly increased the migration of colon cancer cells via sialylation of integrin β1. Here, we further investigated the mechanisms underlying ST6Gal I cleavage, solubilization and release from cells, and addressed its functions, focusing primarily on cancer cell migration.</p> <p>Methods</p> <p>We performed immunoblotting and lectin affinity assay to analyze the expression of ST6 Gal I and level of sialylated integrin β1. After ionizing radiation, migration of cells was measured by in vitro migration assay. α2, 6 sialylation level of cell surface was analyzed by flow cytometry. Cell culture media were concentrated and then analyzed for soluble ST6Gal I levels using an α2, 6 sialyltransferase sandwich ELISA.</p> <p>Result</p> <p>We found that ST6Gal I was cleaved by BACE1 (β-site amyloid precursor protein-cleaving enzyme), which was specifically overexpressed in response to IR. The soluble form of ST6Gal I, which also has sialyltransferase enzymatic activity, was cleaved from the Golgi membrane and then released into the culture media. Both non-cleaved and cleaved forms of ST6Gal I significantly increased colon cancer cell migration in a sialylation-dependent manner. The pro-migratory effect of the non-cleaved form of ST6Gal I was dependent on integrin β1 sialylation, whereas that of the cleaved form of ST6Gal I was not, suggesting that other intracellular sialylated molecules apart from cell surface molecules such as integrin β1 might be involved in mediating the pro-migratory effects of the soluble form of ST6Gal I. Moreover, production of soluble form ST6Gal I by BACE 1 inhibited integrin β1 sialylation and migration by Golgi-anchored form of ST6Gal I.</p> <p>Conclusions</p> <p>Our results suggest that soluble ST6Gal I, possibly in cooperation with the Golgi-bound form, may participate in cancer progression and metastasis prior to being secreted from cancer cells.</p

Emerging themes to support ambitious UK marine biodiversity conservation

Healthy marine ecosystems provide a wide range of resources and services that support life on Earth and contribute to human wellbeing. Marine Protected Areas (MPAs) are accepted as an important tool for the restoration and maintenance of marine ecosystem structure, function, health and ecosystem integrity through the conservation of significant species, habitats, or entire ecosystems. In recent years there has been a rapid expansion in the area of ocean designated as an MPA. Despite this progress in spatial protection targets and the progressive knowledge of the essential interdependence between the human and the ocean system, marine biodiversity continues to decline, placing in jeopardy the range of ecosystem services benefits humans rely on. There is a need to address this shortcoming. Ambitious marine conservation:• Requires a shift from managing individual marine features within MPAs to whole-sites to enable repair and renewal of marine systems;• Reflects an ambition for sustainable livelihoods by fully integrating fisheries management with conservation (Ecosystem Based Fisheries Management) as the two are critically interdependent;• Establishes a world class and cost effective ecological and socio-economic monitoring and evaluation framework that includes the use of controls and sentinel sites to improve sustainability in marine management; and• Challenges policy makers and practitioners to be progressive by integrating MPAs into the wider seascape as critical functional components rather than a competing interest and move beyond MPAs as the only tool to underpin the benefits derived from marine ecosystems by identifying other effective area-based conservation measures (OECMs) to establish synergies with wider governance frameworks

Nutrition support in cancer patients: a brief review and suggestion for standard indications criteria

The indications of nutrition support in cancer patients have been subject to controversy. Most studies address the effects of the method in increasing the survival or the tumor response rate. Few studies have focused on the effects in improving quality of life. After a brief review, we described the results of a study, which evaluated the effects of protein-caloric supplementation on the quality of life parameters in a group of head and neck cancer patients submitted to radiotherapy. The results support the suggestion of creating standard criteria to indicate nutrition support in cancer patients. Based on our findings, nutrition support should be indicated for cancer patients considering the potential effects to improve the quality of life

Body composition in male elite athletes, comparison of bioelectrical impedance spectroscopy with dual energy X-ray absorptiometry

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to compare body composition results from bioelectrical spectroscopy (BIS) with results from dual energy X-ray absorptiometry (DXA) in a population of male elite athletes. Body composition was assessed using DXA (Lunar Prodigy, GE Lunar Corp., Madison, USA) and BIS (Hydra 4200, Xitron Technologies Inc, San Diego, California, USA) at the same occasion. Agreement between methods was assessed using paired t-tests and agreement-plots.</p> <p>Results</p> <p>Thirty-three male elite athletes (soccer and ice hockey) were included in the study. The results showed that BIS underestimates the proportion of fat mass by 4.6% points in the ice hockey players. In soccer players the BIS resulted in a lower mean fat mass by 1.1% points. Agreement between the methods at the individual level was highly variable.</p> <p>Conclusion</p> <p>Body composition results assessed by BIS in elite athletes should be interpreted with caution, especially in individual subjects. BIS may present values of fat mass that is either higher or lower than fat mass assessed by DXA, independent of true fat content of the individual.</p