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

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

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

Variation of dipole moment function of O-H bond of t-butanol with the nature of solvent and its temperature

The intermolecular influence on dipole moment function is evaluated for O-H bond of t-butanol in different nonpolar solvents at temperatures ranging from 10° to 60°C employing IR band intensities of fundamental and first overtone bands. Two sets of dipole moment derivatives have been calculated corresponding to - and +- combinations of the transition moment matrix elements R10 and R20, the values for ++ and -+ combinations are equal in magnitude to those for - and +- combinations, respectively and opposite in signs. In general the dipole moment derivatives increase on lowering the temperature as well as with increasing molecular interactions with the solvent molecules. Dipole moment plots with dimensionless coordinate ξ [=(r-re)/re, where r and re are internuclear distances during vibration and at equilibrium, respectively] are reported for various systems considered. It is found that for +- combination the dipole moment maximum shifts to higher internuclear distances when polarisation of the solute molecules is increased by lowering of temperature or increase in molecular interactions between solute and solvent molecules. A reverse trend is observed for - combination.- The OH band of t-butanol vapor has been measured