A computer-generated supercoiled model of the pUC19 plasmid

DNA models have become a powerful tool in the simulation of radiation-induced molecular damage. Here, a computer code was developed which calculates the coordinates of individual atoms in supercoiled plasmid DNA. In this prototype study, the known base-pair sequence of the pUC19 plasmid has been utilized. The model was built in a three-step process. Firstly, a Monte Carlo simulation was performed to shape a segment chain skeleton. Checks on elastic energy, distance and unknotting were applied. The temperature was considered in two different ways: (1) it was kept constant at 293 K and (2) it was gradually reduced from 350 K to less than 10 K. Secondly, a special smoothing procedure was introduced here to remove the edges from the segment chain without changing the total curve length while avoiding the production of overshooting arcs. Finally, the base pair sequence was placed along the smoothed segment chain and the positions of all the atoms were calculated. As a first result, a few examples of the supercoiled plasmid models will be presented, demonstrating the strong influence of appropriate control of the system temperature

Efficacy and safety of intravenous ferric carboxymaltose compared with oral iron for the treatment of iron deficiency anaemia in women after childbirth in Tanzania: a parallelgroup, open-label, randomised controlled phase 3 trial

Background: Iron deficiency anaemia is of major concern in low-income settings, especially for women of childbearing age. Oral iron substitution efficacy is limited by poor compliance and iron depletion severity. We aimed to assess the efficacy and safety of intravenous ferric carboxymaltose versus oral iron substitution following childbirth in women with iron deficiency anaemia in Tanzania. Methods: This parallel-group, open-label, randomised controlled phase 3 trial was done at Bagamoyo District Hospital and Mwananyamala Hospital, Tanzania. Eligible participants were close to delivery and had iron deficiency anaemia defined as a haemoglobin concentration of less than 110 g/L and a ferritin concentration of less than 50 μg/L measured within 14 days before childbirth. Participants were randomly assigned 1:1 to receive intravenous ferric carboxymaltose or oral iron, stratified by haemoglobin concentration and site. Intravenous ferric carboxymaltose was administered at a dose determined by the haemoglobin concentration and bodyweight (bodyweight 35 kg to <70 kg and haemoglobin ≥100 g/L: 1000 mg in one dose; bodyweight 35 kg to <70 kg and haemoglobin <100 g/L, or bodyweight ≥70 kg and haemoglobin ≥100 g/L: 1500 mg in two doses at least 7 days apart; bodyweight ≥70 kg and haemoglobin 115 g/L) at 6 weeks. Follow-up visits were at 6 weeks, and 3, 6, and 12 months. Analyses were done in the modified intention-totreat population of participants who had a 6-week haemoglobin concentration result, using logistic and linear regression models for binary and continuous outcomes, adjusted for baseline haemoglobin concentration and site. This trial is registered with ClinicalTrials.gov, NCT02541708. Findings: Between Oct 8, 2015, and March 14, 2017, 533 individuals were screened and 230 were enrolled and randomly assigned to a study group (114 to intravenous iron, 116 to oral iron). At 6 weeks, 94 (82%) participants in the intravenous iron group and 92 (79%) in the oral iron group were assessed for the primary outcome. 75 (80%) participants in the intravenous iron group and 47 (51%) in the oral iron group had normalised haemoglobin (odds ratio 4·65, 95% CI 2·33-9·27). There were two mild to moderate infusion-related adverse events; and five serious adverse events (three in the intravenous iron group, two in the oral iron group), unrelated to the study medication. Interpretation: Intravenous iron substitution with ferric carboxymaltose was safe and yielded a better haemoglobin response than oral iron. To our knowledge, this is the first study to provide evidence of the benefits and safety of intravenous iron substitution in a low-income setting

Effectiveness of Nifurtimox Eflornithine Combination Therapy (NECT) in T. b. gambiense second stage sleeping sickness patients in the Democratic Republic of Congo: report from a field study

BACKGROUND: Nifurtimox-eflornithine combination therapy (NECT) for the treatment of second stage gambiense human African trypanosomiasis (HAT) was added to the World Health Organization's Essential Medicines List in 2009 after demonstration of its non-inferior efficacy compared to eflornithine therapy. A study of NECT use in the field showed acceptable safety and high efficacy until hospital discharge in a wide population, including children, pregnant and breastfeeding women, and patients with a HAT treatment history. We present here the effectiveness results after the 24-month follow-up visit. METHODOLOGY/PRINCIPAL FINDINGS: In a multicenter, open label, single arm phase IIIb study, second stage gambiense HAT patients were treated with NECT in the Democratic Republic of Congo. Clinical cure was defined 24 months after treatment as survival without clinical and/or parasitological signs of HAT. Of the 629 included patients, 619 (98.4%) were discharged alive after treatment and were examined for the presence of trypanosomes, white blood cell count in cerebro-spinal fluid, and disease symptoms. The clinical cure rate of 94.1% was comparable for all subpopulations analyzed at the 24-month follow-up visit. Self-reported adverse events during follow-up were few and concerned mainly nervous system disorders, infections, and gastro-intestinal disorders. Overall, 28 patients (4.3%) died during the course of the trial. The death of 16 of the 18 patients who died during the follow-up period was assessed as unlikely or not related to NECT. Within 24 months, eight patients (1.3%) relapsed and received rescue treatment. Sixteen patients were completely lost to follow-up. CONCLUSIONS/SIGNIFICANCE: NECT treatment administered under field conditions was effective and sufficiently well tolerated, no major concern arose for children or pregnant or breastfeeding women. Patients with a previous HAT treatment history had the same response as those who were naive. In conclusion, NECT was confirmed as effective and appropriate for use in a broad population, including vulnerable subpopulations. TRIAL REGISTRATION: The trial is registered at ClinicalTrials.gov, number NCT00906880

International cohort study for pediatric Behçet’s Disease: update 2011

PubMe

From Acting What’s next to Speeding Trap: Co-Evolutionary Dynamics of an Emerging Technology-Leader

JEL Classifications: O33, O53, L63[[abstract]]How does technological innovation emerge and evolve? We approach such an inquiry by synthesizing the perspectives of dynamic capabilities and co-evolutionary dynamics to portray organizational routines and multi-phase strategic renewals of an emerging technology-leader. To untangle the emergence of technological innovation, we conducted a longitudinal case study on the first and the largest dedicated semiconductor foundry, TSMC, located in the emerging economy of Taiwan. The firm-case of TSMC illustrates two unique co-evolutionary paths, that is, transforming from industry-latecomer to technology-leader and from process innovation to product innovation. We found multi-motor co-evolutionary dynamics between TSMC and the semiconductor industry, where its co-evolutionary mechanism of managed selection in its creating phase of mature process-innovation (1987-1998) has migrated to hierarchical renewal in its extending phase of advanced process-innovation (1999-2001), and then to holistic renewal in its modifying phase of product-innovation (2002-2007). During such paths, our research discovered a unique type of organizational routines, acting what’s next because TSMC has proactively searched for potential problems sooner than its competitors. However, such routines, although driving technological innovation, also lead to a unique type of success-trap, that is, speeding trap. When an emerging technology-leader fundamentally changes the industrial structures to over-specs, the growth driven by technology speeding may trap such a leader in a loop of over-exploration.[[sponsorship]]The authors are grateful to the research grant from the National Science Council (NSC) in Taiwan. The earlier manuscript of this paper was presented at the 2009 Annual Meeting of Academy of International Business (AIB) in San Diego, USA.[[notice]]補正完畢[[journaltype]]國外[[ispeerreviewed]]Y[[booktype]]紙本[[booktype]]電子版[[countrycodes]]CA

The discovAIR project:a roadmap towards the Human Lung Cell Atlas

The Human Cell Atlas (HCA) consortium aims to establish an atlas of all organs in the healthy human body at single-cell resolution to increase our understanding of basic biological processes that govern development, physiology and anatomy, and to accelerate diagnosis and treatment of disease. The lung biological network of the HCA aims to generate the Human Lung Cell Atlas as a reference for the cellular repertoire, molecular cell states and phenotypes, and the cell-cell interactions that characterise normal lung homeostasis in healthy lung tissue. Such a reference atlas of the healthy human lung will facilitate mapping the changes in the cellular landscape in disease. The discovAIR project is one of six pilot actions for the HCA funded by the European Commission in the context of the H2020 framework program. DiscovAIR aims to establish the first draft of an integrated Human Lung Cell Atlas, combining single-cell transcriptional and epigenetic profiling with spatially resolving techniques on matched tissue samples, as well as including a number of chronic and infectious diseases of the lung. The integrated Lung Cell Atlas will be available as a resource for the wider respiratory community, including basic and translational scientists, clinical medicine, and the private sector, as well as for patients with lung disease and the interested lay public. We anticipate that the Lung Cell Atlas will be the founding stone for a more detailed understanding of the pathogenesis of lung diseases, guiding the design of novel diagnostics and preventive or curative interventions

Surgery for benign insulinoma: An international review

In a multiinstitutional review, data on 396 patients with benign solitary or multiple insulinomas operated on in 15 centers were collected. In these 396 patients, 419 laparotomies (375 primary procedures and 44 reoperations) were performed. The rate of unnecessary laparotomies was 1.7%. Complications occurred after 132 operations (31.5%), requiring 27 reinterventions (6.4%). Ten (2%) patients died within 30 days of surgery. The success rate of first procedures in the centers was 94.9%. After reoperation, all but 2 (99.5%) of these patients were cured. The overall cure rate including those patients who had their primary operations elsewhere was 97.5% . Compilant les dossiers de 15 établissements internationaux, nous avons colligé les données concernant 396 patients présentant un insulinome bénin unique ou multiple, opérés. Chez ces 396 patients, 419 laparotomies (375 interventions de première intention et 44 reprises) ont été effectuées. Le taux de laparotomie inutile était de 1.7%. Des complications sont intervenues à la suite de 132 opérations (31.5%), nécessitant 27 réinterventions (6.4%). Dix (2%) patients sont morts dans les trente jours après l'acte chirurgical. Le taux de succès des interventions de première intention dans les centres de l'étude était de 94.9%. Après réinterventions, tous les patients sauf 2 (99.5%) ont été guéris. Le taux global de guérison, y compris les patients ayant été opérés une première fois ailleurs, était de 97.5%. En una revisión multiinstitucional se recolectaron los datos sobre 396 pacientes con insulinomas benignos solitarios o múltiples operados en 15 centros. En estos 396 pacientes se efectuaron 419 laparotomías (375 procedimientos primarios y 44 reoperaciones). Se registró una tasa de laparotomías innecesarias de 1.7%; se presentaron complicaciones después de 132 operaciones (31.5%), las cuales requirieron 27 reintervenciones (6.4%). Diez (2%) pacientes murieron dentro de los primeras 30 días después de la cirugía. La tasa de éxito del procedimiento primario realizado en estos centros fue 94.9%. Después de las reoperaciones la totalidad de los pacientes, menos 2 (99.5%), fueron curados. La tasa global de curación, incluyendo los que tuvieron su operación primaria por fuera de los centros del estudio, fue 97.5%.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41289/1/268_2005_Article_BF01658536.pd