Gene and whole genome analyses reveal that the mycobacterial strain JS623 is not a member of the species Mycobacterium smegmatis

Unexpected differences were found between the genome of strain JS623, used in bioremediation studies, and the genome of strain mc2155, a model organism for investigating basic biology of mycobacteria. Both strains are currently assigned in the databases to the species Mycobacterium smegmatis and, consequently, the environmental isolate JS623 is increasingly included as a representative of that species in comparative genomebased approaches aiming at identifying distinctive traits of the different members of the genus Mycobacterium. We applied traditional molecular taxonomic procedures – inference of single and concatenated gene trees – to re-evaluate the membership of both strains to the same species, adopting the latest accepted cut-off values for species delimitation. Additionally, modern whole genome-based in silico methods where performed in a comprehensive molecular phylogenetic analysis of JS623 and other members of the genus Mycobacterium. These analyses showed that all relevant genome parameters of JS623 clearly separate this strain from M. smegmatis. The strain JS623 should be corrected as Mycobacterium sp. not only in the literature but, even more importantly, in the database entries, as inclusion of the genome wrongly attributed to the M. smegmatis species in comparative studies will result in misleading conclusionsThis work has been partially supported by funds from the International Cooperation UAM-Banco Santander and Latin America (CEAL-UAM) and the Spanish Ministry of Health (AES, PI13-01218) (MJG) as well as BFU2014-52070-C2-1 1 from the Spanish Government (SG

Disk wakes in nonlinear stratification

Nonlinearity of density stratification modulates buoyancy effects. We report results from a body-inclusive large eddy simulation (LES) of a wake in nonlinear stratification, specifically for a circular disk at diameter-based Reynolds number ($Re$) of $5000$. Five density profiles are considered; the benchmark has linear stratification and the other four have hyperbolic tangent profiles to model a pycnocline. The disk moves inside the central core of the pycnocline in two of those four cases and, in the other two cases with {a} shifted density profile, the disk moves partially/completely outside the pycnocline. The maximum buoyancy frequency ($N_{max}$) for all the profiles is the same. The first part of the study investigates the centered cases. Nonuniform stratification results in increasing wake turbulence relative to the benchmark owing to reduced suppression of turbulence production as well as the wave trapping in the pycnocline. Steady lee waves are also quantified to understand limitations of linear theory. The second part pays attention to the effect of a relative shift between the pycnocline and the disk. The wake defect velocity decays faster in the cases with a shift. The effect of disk location on the Kelvin wake waves (a family of steady waves within the pycnocline) and its modal form is obtained and explained by solving the Taylor-Goldstein equation. The family of unsteady internal gravity waves that are generated by the wake is also studied and the effect of disk shift is quantified.Comment: 23 pages, 15 plots, submitted to Journal of Fluid Mechanic

Photodynamic therapy of cutaneous T-cell lymphoma cell lines mediated by 5-aminolevulinic acid and derivatives

The delta-amino acid 5-aminolevulinic acid (ALA), is the precursor of the endogenous photosensitiser Protoporphyrin IX (PpIX), and is currently approved for Photodynamic Therapy (PDT) of certain superficial cancers. However, ALA-PDT is not very effective in diseases in which T-cells play a significant role. Cutaneous T-cell lymphomas (CTCL) is a group of non-Hodgkin malignant diseases, which includes mycosis fungoides (MF) and Sézary syndrome (SS). In previous work, we have designed new ALA esters synthesised by three-component Passerini reactions, and some of them showed higher performance as compared to ALA. This work aimed to determine the efficacy as pro-photosensitisers of five new ALA esters of 2-hydroxy-N-arylacetamides (1f, 1 g, 1 h, 1i and 1 k) of higher lipophilicity than ALA in Myla cells of MF and HuT-78 cells of SS. We have also tested its effectiveness against ALA and the already marketed ALA methyl ester (Me-ALA) and ALA hexyl ester (He-ALA). Both cell Myla and SS cells were effectively and equally photoinactivated by ALA-PDT. Besides, the concentration of ALA required to induce half the maximal porphyrin synthesis was 209 μM for Myla and 169 μM for HuT-78 cells. As a criterion of efficacy, we calculated the concentration of the ALA derivatives necessary to induce half the plateau porphyrin values obtained from ALA. These values were achieved at concentrations 4 and 12 times lower compared to ALA, according to the derivative used. For He-ALA, concentrations were 24 to 25 times lower than required for ALA for inducing comparable porphyrin synthesis in both CTCL cells. The light doses for inducing 50% of cell death (LD50) for He-ALA, 1f, 1 g, 1 h and 1i were around 18 and 25 J/cm2 for Myla and HuT-78 cells respectively, after exposure to 0.05 mM concentrations of the compounds. On the other hand, the LD50s for the compound 1 k were 40 and 57 J/cm2 for Myla and HuT-78, respectively. In contrast, 0.05 mM of ALA and Me-ALA did not provoke photokilling since the concentration employed was far below the porphyrin saturation point for these compounds. Our results suggest the potential use of ALA derivatives for topical application in PDT treatment of MF and extracorporeal PDT for the depletion of activated T-cells in SS

Acceptance and commitment therapy for adults with advanced cancer (CanACT): study protocol for a feasibility randomised controlled trial

BACKGROUND: One-third of people with cancer experience psychological distress and may suppress distressing thoughts, emotions, and concerns, leading to further problems. Conventional psychological treatments reduce distress by problem solving, but in advanced cancer, when ill health is progressive and death may be approaching, physical and psychological difficulties are complex and have no simple solutions. Acceptance and Commitment Therapy encourages acknowledgement and acceptance of mental experiences, increasing people's ability to work with problems that cannot be solved. Previous pilot work in advanced cancer confirms that distress can be associated with an avoidance of experiencing uncomfortable thoughts and emotions. METHODS/DESIGN: This feasibility randomised controlled trial of Acceptance Commitment Therapy aims to establish parameters for a larger trial. Fifty-four participants with advanced cancer will be randomly allocated to up to eight sessions (each 1 hour) of Acceptance Commitment Therapy or a talking control. Participants will be recruited from those attending outpatient services and hospice day care at three specialist palliative care units in North and East London, United Kingdom. The primary outcome is a measure of functioning in four areas of life (physical, social/family, emotional, and general activity) using the Functional Assessment of Cancer Therapies - General questionnaire at 3 months after randomisation. Secondary outcomes are (i) acceptance using the Acceptance and Action Questionnaire; (ii) psychological distress using the Kessler Psychological Distress Scale; (iii) physical functioning using a timed walk and sit-to-stand test; and (iv) quality of life measures including the Euroqol-5 Dimensions and ICECAP Supportive Care measures. Qualitative data will be collected at 3 months to explore the participants' experiences of the trial and therapy. Data will be collected on the costs of care. DISCUSSION: Data generated on the recruitment, retention, and experience of the interventions and the usefulness of the outcome measures will inform the adaptations required and whether changes in function are consistent with existing data when planning for a sufficiently powered randomised controlled trial. TRIAL REGISTRATION: ISRCTN13841211 (registered 22 July 2015)

Are short food supply chains more environmentally sustainable than long chains? a life cycle assessment (LCA) of the eco-efficiency of food chains in selected EU countries

Improving the eco-efficiency of food systems is one of the major global challenges faced by the modern world. Short food supply chains (SFSCs) are commonly regarded to be less harmful to the environment, among various reasons, due to their organizational distribution and thus the shortened physical distance between primary producers and final consumers. In this paper, we empirically test this hypothesis, by assessing and comparing the environmental impacts of short and long food supply chains. Based on the Life Cycle Assessment (LCA) approach, we calculate eco-efficiency indicators for nine types of food distribution chains. The analysis is performed on a sample of 428 short and long food supply chains from six European countries. Our results indicate that, on average, long food supply chains may generate less negative environmental impacts than short chains (in terms of fossil fuel energy consumption, pollution, and GHG emissions) per kg of a given product. The values of eco-efficiency indicators display a large variability across analyzed chains, and especially across different types of SFSCs. The analysis shows that the environmental impacts of the food distribution process are not only determined by the geographical distance between producer and consumer, but depend on numerous factors, including the supply chain infrastructure

Empowering Better End-of-Life Dementia Care (EMBED-Care): A mixed methods protocol to achieve integrated person-centred care across settings

Objectives Globally, the number of people with dementia who have palliative care needs will increase fourfold over the next 40 years. The Empowering Better End‐of‐Life Dementia Care (EMBED‐Care) Programme aims to deliver a step change in care through a large sequential study, spanning multiple work streams. Methods We will use mixed methods across settings where people with dementia live and die: their own homes, care homes, and hospitals. Beginning with policy syntheses and reviews of interventions, we will develop a conceptual framework and underpinning theory of change. We will use linked data sets to explore current service use, care transitions, and inequalities and predict future need for end‐of‐life dementia care. Longitudinal cohort studies of people with dementia (including young onset and prion dementias) and their carers will describe care transitions, quality of life, symptoms, formal and informal care provision, and costs. Data will be synthesised, underpinned by the Knowledge‐to‐Action Implementation Framework, to design a novel complex intervention to support assessment, decision making, and communication between patients, carers, and inter‐professional teams. This will be feasibility and pilot tested in UK settings. Patient and public involvement and engagement, innovative work with artists, policymakers, and third sector organisations are embedded to drive impact. We will build research capacity and develop an international network for excellence in dementia palliative care. Conclusions EMBED‐Care will help us understand current and future need, develop novel cost‐effective care innovations, build research capacity, and promote international collaborations in research and practice to ensure people live and die well with dementia