Rifampicina y biodisponibilidad en productos combinados

The drug rifampicin (R) is used as a first line antibiotic treatment for tuberculosis (TB), together withIsoniazide (H), Pyrazinamide (Z) and Ethambutol (E). According to recent statistics, there has been anincrease in TB on a worldwide scale, with the main causes being: monotherapies, the appearance ofresistant microorganisms, the lack of effective preventative programs, non-compliance to treatment andmistaken dosage schedules. The world health organisation (WHO) and the International Union AgainstTuberculosis and Lung Diseases(IUTALD) declared a state of emergency with respect to the disease andestablished programs to increase compliance to therapy and to reduce the incidence of problems arisingfrom such. Along these lines, a list of first line drug therapy treatments were established, whichincluded R, Z, H & E combinations at fixed dosage combinations (FDC), permitting safe combinedadministrations of the drugs at correct dosage levels. These fixed dose combinations have been officiallyrecommended by the WHO in the treatment of TB. However, as has been widely recognised in numerousscientific publications, in such formulations, there are factors that alter the bioavailability of R. Theobjective of this work has been to study the most relevant aspects concerning R bioavailability alterationsand to consider possible solutions to the problem.La rifampicina (R) es un antibiótico de primera elección en el tratamiento de la tuberculosis (TB) juntoa la Isoniazida (H), Pirazinamida (Z) y Etambutol (E). De acuerdo a las últimas estadísticas, la TBaumentó a nivel mundial y entre las causas más citadas figuran: las monoterapias, la aparición demicroorganismos resistentes, la carencia de programas efectivos, el incumplimiento en el tratamiento ylas dosis erróneas. La Organización Mundial de la Salud (OMS) y la Unión Internacional Contra laTuberculosis y Enfermedades de Pulmón (IUATLD) declararon a la enfermedad en emergencia mundialy establecieron programas terapéuticos para asegurar el cumplimiento y disminuir los problemas relacionadosa la terapia. Sobre esta base, figura en la lista oficial la asociación de los cuatro fármacos deprimera línea R, Z, H y E combinados en dosis fijas (FDC) que permiten la administración conjunta delos mismos y, en las dosis correctas. Los productos FDC son recomendados oficialmente por la OMSpara el tratamiento de la TB. No obstante existen factores que alteran la biodisponibilidad de la R enestas formulaciones, hecho ampliamente reconocido en publicaciones científicas. El objetivo de estetrabajo es estudiar los aspectos más relevantes que alteran la biodisponibilidad de la R en los productosFDC y plantear posibles soluciones al problema

Rifampicina y biodisponibilidad en productos combinados

The drug rifampicin (R) is used as a first line antibiotic treatment for tuberculosis (TB), together withIsoniazide (H), Pyrazinamide (Z) and Ethambutol (E). According to recent statistics, there has been anincrease in TB on a worldwide scale, with the main causes being: monotherapies, the appearance ofresistant microorganisms, the lack of effective preventative programs, non-compliance to treatment andmistaken dosage schedules. The world health organisation (WHO) and the International Union AgainstTuberculosis and Lung Diseases(IUTALD) declared a state of emergency with respect to the disease andestablished programs to increase compliance to therapy and to reduce the incidence of problems arisingfrom such. Along these lines, a list of first line drug therapy treatments were established, whichincluded R, Z, H & E combinations at fixed dosage combinations (FDC), permitting safe combinedadministrations of the drugs at correct dosage levels. These fixed dose combinations have been officiallyrecommended by the WHO in the treatment of TB. However, as has been widely recognised in numerousscientific publications, in such formulations, there are factors that alter the bioavailability of R. Theobjective of this work has been to study the most relevant aspects concerning R bioavailability alterationsand to consider possible solutions to the problem.La rifampicina (R) es un antibiótico de primera elección en el tratamiento de la tuberculosis (TB) juntoa la Isoniazida (H), Pirazinamida (Z) y Etambutol (E). De acuerdo a las últimas estadísticas, la TBaumentó a nivel mundial y entre las causas más citadas figuran: las monoterapias, la aparición demicroorganismos resistentes, la carencia de programas efectivos, el incumplimiento en el tratamiento ylas dosis erróneas. La Organización Mundial de la Salud (OMS) y la Unión Internacional Contra laTuberculosis y Enfermedades de Pulmón (IUATLD) declararon a la enfermedad en emergencia mundialy establecieron programas terapéuticos para asegurar el cumplimiento y disminuir los problemas relacionadosa la terapia. Sobre esta base, figura en la lista oficial la asociación de los cuatro fármacos deprimera línea R, Z, H y E combinados en dosis fijas (FDC) que permiten la administración conjunta delos mismos y, en las dosis correctas. Los productos FDC son recomendados oficialmente por la OMSpara el tratamiento de la TB. No obstante existen factores que alteran la biodisponibilidad de la R enestas formulaciones, hecho ampliamente reconocido en publicaciones científicas. El objetivo de estetrabajo es estudiar los aspectos más relevantes que alteran la biodisponibilidad de la R en los productosFDC y plantear posibles soluciones al problema

Mexico City and the biogeochemistry of global urbanization

Mexico City is far advanced in its urban evolution, and cities in currently developing nations may soon follow a similar course. This paper investigates the strengths and weaknesses of infrastructures for the emerging megacities. The major driving force for infrastructure change in Mexico City is concern over air quality. Air chemistry data from recent field campaigns have been used to calculate fluxes in the atmosphere of the Valley of Mexico, for compounds that are important to biogeochemistry including methane (CH4), carbon monoxide (CO), nonmethane hydrocarbons (NMHCs), ammonia (NH3), sulfur dioxide (SO2), nitrogen oxides (NOx and NOy), soot, and dust. Leakage of liquified petroleum gas approached 10% during sampling periods, and automotive pollutant sources in Mexico City were found to match those in developed cities, despite a lower vehicle-to-person ratio of 0.1. Ammonia is released primarily from residential areas, at levels sufficient to titrate pollutant acids into particles across the entire basin. Enhancements of reduced nitrogen and hydrocarbons in the vapor phase skew the distribution of NOy species towards lower average deposition velocities. Partly as a result, downwind nutrient deposition occurs on a similar scale as nitrogen fixation across Central America, and augments marine nitrate upwelling. Dust suspension from unpaved roads and from the bed of Lake Texcoco was found to be comparable to that occurring on the periphery of the Sahara, Arabian, and Gobi deserts. In addition, sodium chloride (NaCl) in the dust may support heterogeneous chlorine oxide (ClOx) chemistry. The insights from our Mexico City analysis have been tentatively applied to the upcoming urbanization of Asia

Complete re-utilization of waste concretes–Valorisation pathways and research needs

Global demand for buildings and infrastructure is extremely high as provision of shelter, sanitation and healthcare are paramount to safeguard the world's growing population. Concrete is a preferred construction material to meet this demand, but its production is leading to overexploitation of natural gravel and sand, causing an environmental crisis in regions where these materials are extracted unsustainably. Waste concrete is available globally, particularly in regions with fast growth of the built environment, and those struck by coordinated attacks, earthquakes or severe weather events. Waste concrete has mainly been used for producing recycled aggregates; however, its full recycling is still not practiced. Alternative uses include applications as fine recycled aggregates, supplementary cementitious materials, filler, and feedstocks for clinker production. These technologies still face challenges concerning their adoption and eco-efficiency. Restricted knowledge and operational barriers have also prevented implementation of beneficiation technologies for complete re-recycling of waste concretes, particularly the fine fractions produced during crushing. Despite these issues, it is recognised that the complete utilization of waste concrete offers unique opportunities for supply chain security, reducing natural resources consumption and enabling to move towards a Circular Economy. Harmonizing current practices for the treatment of waste concrete and the by-products generated during their processing, is a first step toward policy and standards development to enable their widespread use. This critical discussion addresses challenges and opportunities, as well as facilitation strategies needed to progress the complete re-utilization of waste concrete as a valuable resource for creating sustainable future infrastructure

Leg length, skull circumference, and the incidence of dementia in Latin America and China: A 10/66 population-based cohort study

\ua9 2018 Prince et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background Adult leg length is influenced by nutrition in the first few years of life. Adult head circumference is an indicator of brain growth. Cross-sectional studies indicate inverse associations with dementia risk, but there have been few prospective studies. Methods Population-based cohort studies in urban sites in Cuba, Dominican Republic Puerto Rico and Venezuela, and rural and urban sites in Peru, Mexico and China. Sociodemographic and risk factor questionnaires were administered to all participants, and anthropometric measures taken, with ascertainment of incident dementia, and mortality, three to five years later. Results Of the original at risk cohort of 13,587 persons aged 65 years and over, 2,443 (18.0%) were lost to follow-up; 10,540 persons with skull circumference assessments were followed up for 40,466 person years, and 10,400 with leg length assessments were followed up for 39,954 person years. There were 1,009 cases of incident dementia, and 1,605 dementia free deaths. The fixed effect pooled meta-analysed adjusted subhazard ratio (ASHR) for leg length (highest vs. lowest quarter) was 0.80 (95% CI, 0.66–0.97) and for skull circumference was 1.02 (95% CI, 0.84–1.25), with no heterogeneity of effect between sites (I2 = 0%). Leg length measurements tended to be shorter at follow-up, particularly for those with baseline cognitive impairment and dementia. However, leg length change was not associated with dementia incidence (ASHR, per cm 1.006, 95% CI 0.992–1.020), and the effect of leg length was little altered after adjusting for baseline frailty (ASHR 0.82, 95% CI 0.67–0.99). A priori hypotheses regarding effect modification by gender or educational level were not supported. However, the effect of skull circumference was modified by gender (M vs F ASHR 0.86, 95% CI 0.75–0.98), but in the opposite direction to that hypothesized with a greater protective effect of larger skull dimensions in men. Conclusions Consistent findings across settings provide quite strong support for an association between adult leg length and dementia incidence in late-life. Leg length is a relatively stable marker of early life nutritional programming, which may confer brain reserve and protect against neu-rodegeneration in later life through mitigation of cardiometabolic risk. Further clarification of these associations could inform predictive models for future dementia incidence in the context of secular trends in adult height, and invigorate global efforts to improve childhood nutrition, growth and development

Successful new product development by optimizing development process effectiveness in highly regulated sectors: the case of the Spanish medical devices sector

Rapid development and commercialization of new products is of vital importance for small and medium sized enterprises (SME) in regulated sectors. Due to strict regulations, competitive advantage can hardly be achieved through the effectiveness of product concepts only. If an SME in a highly regulated sector wants to excell in new product development (NPD) performance, the company should focus on the flexibility, speed, and productivity of its NPD function: i.e. the development process effectiveness. Our main research goals are first to explore if SMEs should focus on their their development process effectiveness rather than on their product concept effectiveness to achieve high NPD performance; and second, to explore whether a shared pattern in the organization of the NPD function can be recognized to affect NPD performance positively. The medical devices sector in Spain is used as an example of a\ud highly regulated sector. A structured survey among 11 SMEs, of which 2 were studied also as in in-depth case studies, led to the following results. First of all, indeed the companies in the dataset which focused on the effectiveness of their development process, stood out in NPD performance. Further, the higher performing companies did have a number of commonalities in the organisation of their NPD function: 1) The majority of the higher performing firms had an NPD strategy characterized by a predominantly incremental project portfolio.\ud 2) a) Successful firms with an incremental project portfolio combined this with a functional team structure b) Successful firms with a radical project portfolio combined this with a heavyweight or autonomous team structure.\ud 3) A negative reciprocal relationship exists between formalization of the NPD processes and the climate of the NPD function, in that a formalized NPD process and an innovative climate do not seem to reinforce each other. Innovative climate combined with an informal NPD process does however contribute positively to NPD performance. This effect was stronger in combination with a radical project portfolio. The highest NPD performance was measured for companies focusing mainly on incremental innovation. It is argued that in highly regulated sectors, companies with an incremental product portfolio would benefit from employing a functional structure. Those companies who choose for a more radical project portfolio in highly regulated sectors should be aware\ud that they are likely to excell only in the longer term by focusing on strategic flexibility. In their NPD organization, they might be well advised to combine informal innovation processes with an innovative climate

Testing in the incremental design and development of complex products

Testing is an important aspect of design and development which consumes significant time and resource in many companies. However, it has received less research attention than many other activities in product development, and especially, very few publications report empirical studies of engineering testing. Such studies are needed to establish the importance of testing and inform the development of pragmatic support methods. This paper combines insights from literature study with findings from three empirical studies of testing. The case studies concern incrementally developed complex products in the automotive domain. A description of testing practice as observed in these studies is provided, confirming that testing activities are used for multiple purposes depending on the context, and are intertwined with design from start to finish of the development process, not done after it as many models depict. Descriptive process models are developed to indicate some of the key insights, and opportunities for further research are suggested

Multimodal Functional Network Connectivity: An EEG-fMRI Fusion in Network Space

EEG and fMRI recordings measure the functional activity of multiple coherent networks distributed in the cerebral cortex. Identifying network interaction from the complementary neuroelectric and hemodynamic signals may help to explain the complex relationships between different brain regions. In this paper, multimodal functional network connectivity (mFNC) is proposed for the fusion of EEG and fMRI in network space. First, functional networks (FNs) are extracted using spatial independent component analysis (ICA) in each modality separately. Then the interactions among FNs in each modality are explored by Granger causality analysis (GCA). Finally, fMRI FNs are matched to EEG FNs in the spatial domain using network-based source imaging (NESOI). Investigations of both synthetic and real data demonstrate that mFNC has the potential to reveal the underlying neural networks of each modality separately and in their combination. With mFNC, comprehensive relationships among FNs might be unveiled for the deep exploration of neural activities and metabolic responses in a specific task or neurological state