The Complete Genome Sequence of Cupriavidus metallidurans Strain CH34, a Master Survivalist in Harsh and Anthropogenic Environments

Many bacteria in the environment have adapted to the presence of toxic heavy metals. Over the last 30 years, this heavy metal tolerance was the subject of extensive research. The bacterium Cupriavidus metallidurans strain CH34, originally isolated by us in 1976 from a metal processing factory, is considered a major model organism in this field because it withstands milli-molar range concentrations of over 20 different heavy metal ions. This tolerance is mostly achieved by rapid ion efflux but also by metal-complexation and -reduction. We present here the full genome sequence of strain CH34 and the manual annotation of all its genes. The genome of C. metallidurans CH34 is composed of two large circular chromosomes CHR1 and CHR2 of, respectively, 3,928,089 bp and 2,580,084 bp, and two megaplasmids pMOL28 and pMOL30 of, respectively, 171,459 bp and 233,720 bp in size. At least 25 loci for heavy-metal resistance (HMR) are distributed over the four replicons. Approximately 67% of the 6,717 coding sequences (CDSs) present in the CH34 genome could be assigned a putative function, and 9.1% (611 genes) appear to be unique to this strain. One out of five proteins is associated with either transport or transcription while the relay of environmental stimuli is governed by more than 600 signal transduction systems. The CH34 genome is most similar to the genomes of other Cupriavidus strains by correspondence between the respective CHR1 replicons but also displays similarity to the genomes of more distantly related species as a result of gene transfer and through the presence of large genomic islands. The presence of at least 57 IS elements and 19 transposons and the ability to take in and express foreign genes indicates a very dynamic and complex genome shaped by evolutionary forces. The genome data show that C. metallidurans CH34 is particularly well equipped to live in extreme conditions and anthropogenic environments that are rich in metals

Robotically driven construction of buildings: Exploring on-demand building components production

Robotically Driven Construction of Buildings (RDCB) is an exploration into design to production solutions for robotically driven construction of buildings initiated by the faculties of Civil Engineering and Architecture, TU Delft and Architecture, TU Eindhoven and implemented 2014 within the 3TU Lighthouse framework. The aim of was to involve the disciplines of architecture, robotics, materials science, and structural design in order to integrate knowledge from the individual disciplines and develop new numerically controlled manufacturing techniques and building-design optimisation methods for adding creative value to buildings in a cost-effective and sustainable way.RDCB builds up on expertise developed at Hyperbody with respect to applications of robotics in architecture and this paper presents the contribution of the Robotic Building team from Hyperbody, Faculty of Architecture, TU Delft to the RDCB project. The contribution is in line with Europe’s aim to improve material and energy efficiency of buildings and efficiency of construction processes. Robotically driven construction and customised building materials have the potential to realise this in a cost-effective way and at the same time reduce accidents and health hazards for workers in the building sector. In order to achieve this RDCB is distributing materials as needed and where needed. This requires exploration of a variety of techniques and implies working with customised materials and techniques while finding the best methods of applying materials in the logic of specific force flows or thermal dissipation patterns.RDCB advances multi- and trans-disciplinary knowledge in robotically driven construction by designing and engineering new building systems for the on-demand production of customisable building components (Bier, 2014). The main consideration is that in architecture and building construction the factory of the future employs building materials and components that can be on site robotically processed and assembled

Social pharmaceutical innovation and alternative forms of research, development and deployment for drugs for rare diseases

Rare diseases are associated with difficulties in addressing unmet medical needs, lack of access to treatment, high prices, evidentiary mismatch, equity, etc. While challenges facing the development of drugs for rare diseases are experienced differently globally (i.e., higher vs. lower and middle income countries), many are also expressed transnationally, which suggests systemic issues. Pharmaceutical innovation is highly regulated and institutionalized, leading to firmly established innovation pathways. While deviating from these innovation pathways is difficult, we take the position that doing so is of critical importance. The reason is that the current model of pharmaceutical innovation alone will not deliver the quantity of products needed to address the unmet needs faced by rare disease patients, nor at a price point that is sustainable for healthcare systems. In light of the problems in rare diseases, we hold that re-thinking innovation is crucial and more room should be provided for alternative innovation pathways. We already observe a significant number and variety of new types of initiatives in the rare diseases field that propose or use alternative pharmaceutical innovation pathways which have in common that they involve a diverse set of societal stakeholders, explicitly address a higher societal goal, or both. Our position is that principles of social innovation can be drawn on in the framing and articulation of such alternative pathways, which we term here social pharmaceutical innovation (SPIN), and that it should be given more room for development. As an interdisciplinary research team in the social sciences, public health and law, the cases of SPIN we investigate are spread transnationally, and include higher income as well as middle income countries. We do this to develop a better understanding of the social pharmaceutical innovation field’s breadth and to advance changes ranging from the bedside to system levels. We seek collaborations with those working in such projects (e.g., patients and patient organisations, researchers in rare diseases, industry, and policy makers). We aim to add comparative and evaluative value to social pharmaceutical innovation, and we seek to ignite further interest in these initiatives, thereby actively contributing to them as a part of our work

Redefining craft in an information society

This thesis explores the topic of Craft in an information society, the redefinition of craft that follows is developed through the design of a 3D bio printing laboratory in Nijmegen Netherlands

Triple artemisinin combination therapies: A new paradigm for the treatment of malaria?

Artemisinin Combination Therapies (ACT) are first-line treatments for malaria. The Tracking Resistance to Artemisinin Collaboration (TRAC) mapped the spread of artemisinin resistance in 10 countries in Asia (7) and Africa (3) and described artemisinin resistance in Southeast Asia (SEA). In Cambodia, Thailand, and Vietnam, artemisinin resistance is compounded by partner drug resistance resulting in dihydroartemisininpiperaquine (DHA-PPQ) treatment failure rates of >60%. The TRACII study conducted in 8 countries in Asia (7) and Africa (1) explored the concept of combining an ACT with a third antimalarial drug and assessed efficacy, safety and tolerability of two Triple ACT (TACT): DHA-PPQ+mefloquine (DHA-PPQ+MQ) and artemether-lumefantrine+amodiaquine (AL+AQ). Both TACT were safe, well tolerated and highly efficacious against ACTresistant parasites in SEA. TACT could become standard treatment for malaria worldwide as part of strategies to prevent or delay emergence of drug resistant malaria in regions outside of SEA. A new project titled Development of Triple Artemisinin Combination Therapies (DeTACT) will take a multifaceted approach to assess potential benefits and disadvantages of deploying TACT as first-line antimalarial treatments. In a randomized, controlled, non-inferiority trial, we will compare safety, tolerability and efficacy of dose-optimised artesunate-PPQ+MQ and AL+AQ TACT in blistered co-packages versus ACT+placebo in 13 countries in Asia (5) and Africa (8). The potential of TACT to delay emergence and spread of antimalarial resistance and cost-effectiveness of deploying TACT will be assessed through mathematical modelling. We will address ethical issues such as balancing individual and community disadvantages versus public benefits of introducing TACT in regions where ACT are still efficacious. Market and demand related issues involved in development, implementation and deployment of TACT will be studied to guide future introduction in the global marketplace and communicated to stakeholders via a strategic engagement plan. Development of the project and progress to date will be presented

Social pharmaceutical innovation and alternative forms of research, development and deployment for drugs for rare diseases

Rare diseases are associated with difficulties in addressing unmet medical needs, lack of access to treatment, high prices, evidentiary mismatch, equity, etc. While challenges facing the development of drugs for rare diseases are experienced differently globally (i.e., higher vs. lower and middle income countries), many are also expressed transnationally, which suggests systemic issues. Pharmaceutical innovation is highly regulated and institutionalized, leading to firmly established innovation pathways. While deviating from these innovation pathways is difficult, we take the position that doing so is of critical importance. The reason is that the current model of pharmaceutical innovation alone will not deliver the quantity of products needed to address the unmet needs faced by rare disease patients, nor at a price point that is sustainable for healthcare systems. In light of the problems in rare diseases, we hold that re-thinking innovation is crucial and more room should be provided for alternative innovation pathways. We already observe a significant number and variety of new types of initiatives in the rare diseases field that propose or use alternative pharmaceutical innovation pathways which have in common that they involve a diverse set of societal stakeholders, explicitly address a higher societal goal, or both. Our position is that principles of social innovation can be drawn on in the framing and articulation of such alternative pathways, which we term here social pharmaceutical innovation (SPIN), and that it should be given more room for development. As an interdisciplinary research team in the social sciences, public health and law, the cases of SPIN we investigate are spread transnationally, and include higher income as well as middle income countries. We do this to develop a better understanding of the social pharmaceutical innovation field’s breadth and to advance changes ranging from the bedside to system levels. We seek collaborations with those working in such projects (e.g., patients and patient organisations, researchers in rare diseases, industry, and policy makers). We aim to add comparative and evaluative value to social pharmaceutical innovation, and we seek to ignite further interest in these initiatives, thereby actively contributing to them as a part of our work.Pharmaceutical Sciences, Faculty ofNon UBCReviewedFacultyResearche

Assessing channel changes of the Ganges-Padma River system in Bangladesh using Landsat and hydrological data

© 2016 Elsevier B.V.The Ganga/Ganges1is an important river system in South Asia which supports the life and livelihoods of millions of people both in India and Bangladesh. The system has a number of names throughout its length. Below its confluence with the Brahmaputra at Aricha it is known as the Padma, which in turn merges with the Upper Meghna at Chandpur below which the channel is known as the Lower Meghna. There is a growing concern about this large river system because its channels are subject to frequent migration, threatening engineering structures and resulting in various environmental and social consequences which may be compounded by climatic variability, land use change, and agricultural intensification as the basin experiences rapid population growth. Concerns have been expressed that the construction of a barrage just upstream of the Indo–Bangladesh border has adversely affected the Ganges reach in Bangladesh. Partly in order to investigate this, the planform changes of the Ganges and the Padma within Bangladesh was analysed over the period 1973 to 2011 using multitemporal Landsat images and long–term flow data in eight epochs with an average duration of 4.5 years. The Padma reach is less affected by the barrage and provides a useful control study. Areas of erosion and deposition were determined from sequential changes in the bankline positions. Mean channel width, sinuosity and braiding index were analysed using a Geographic Information System (GIS). Flood frequency, duration and magnitudes were studied using long-term discharge records. Generally, channel planform evaluation indicated that both the Ganges and the Padma experienced contraction, expansion and readjustment in configuration over the last 38 years. Erosion and deposition statistics of the Ganges indicate that 57 km2 of land was lost along the right bank whereas around 59 km2 has been gained along the left bank during the assessment period, suggesting that the erosion and accretion of both banks is roughly balanced with a general movement towards the right bank. The width of the Ganges varied from a maximum of 5.36 to a minimum of 3.23 km during the observation period. Changes to sandbar area are, in general, much more radical than changes to the overall width and area of the channel. Measurement of areas of erosion and accretion showed that both banks of the Padma experienced considerable loss of land. The total net loss for left bank and right bank was 155 and 28 km2, respectively. The Padma is approximately twice the width of the Ganges and the changes to its channel area are not as temporally dynamic as the Ganges. The relationship between bank curvature and erosion/accretion of the river banks for both rivers was analysed and the results contradict established meander theory. Regression analysis between bank erosion rates, annual average discharge and mean flood flow data showed that bank erosion was significantly correlated with annual average discharge for the Padma (r2 = 0.6283) and that the Ganges bank erosion rate is influenced by mean flood flow (r2 = 0.6738). The flood frequency shows generally good stability across the first eight of the nine epochs for the Ganges but for the Padma the frequency showed even greater stability. We were unable to support the widely held belief that the upstream barrage has a deleterious effect on the Ganges but note that there is a slight effect due to the periodic release of sediment through scour sluices

Incidence of severe critical events in paediatric anaesthesia (APRICOT): a prospective multicentre observational study in 261 hospitals in Europe

Background Little is known about the incidence of severe critical events in children undergoing general anaesthesia in Europe. We aimed to identify the incidence, nature, and outcome of severe critical events in children undergoing anaesthesia, and the associated potential risk factors. Methods The APRICOT study was a prospective observational multicentre cohort study of children from birth to 15 years of age undergoing elective or urgent anaesthesia for diagnostic or surgical procedures. Children were eligible for inclusion during a 2-week period determined prospectively by each centre. There were 261 participating centres across 33 European countries. The primary endpoint was the occurence of perioperative severe critical events requiring immediate intervention. A severe critical event was defined as the occurrence of respiratory, cardiac, allergic, or neurological complications requiring immediate intervention and that led (or could have led) to major disability or death. This study is registered with ClinicalTrials.gov, number NCT01878760. Findings Between April 1, 2014, and Jan 31, 2015, 31â127 anaesthetic procedures in 30â874 children with a mean age of 6·35 years (SD 4·50) were included. The incidence of perioperative severe critical events was 5·2% (95% CI 5·0â5·5) with an incidence of respiratory critical events of 3·1% (2·9â3·3). Cardiovascular instability occurred in 1·9% (1·7â2·1), with an immediate poor outcome in 5·4% (3·7â7·5) of these cases. The all-cause 30-day in-hospital mortality rate was 10 in 10â000. This was independent of type of anaesthesia. Age (relative risk 0·88, 95% CI 0·86â0·90; p<0·0001), medical history, and physical condition (1·60, 1·40â1·82; p<0·0001) were the major risk factors for a serious critical event. Multivariate analysis revealed evidence for the beneficial effect of years of experience of the most senior anaesthesia team member (0·99, 0·981â0·997; p<0·0048 for respiratory critical events, and 0·98, 0·97â0·99; p=0·0039 for cardiovascular critical events), rather than the type of health institution or providers. Interpretation This study highlights a relatively high rate of severe critical events during the anaesthesia management of children for surgical or diagnostic procedures in Europe, and a large variability in the practice of paediatric anaesthesia. These findings are substantial enough to warrant attention from national, regional, and specialist societies to target education of anaesthesiologists and their teams and implement strategies for quality improvement in paediatric anaesthesia. Funding European Society of Anaesthesiology