190 research outputs found
Rifampicin resistance after treatment for latent tuberculous infection: A systematic review and meta-analysis
No full textContinuous isoniazid for the treatment of latent tuberculosis infection in people living with HIV
No full textThis systematic review was carried out to determine the effectiveness of continuous isoniazid (given for at least 36 months) for the treatment of latent tuberculosis infection (LTBI) in people living with HIV (PLHIV).
Six databases and HIV and tuberculosis (TB) conference abstract books were searched for randomized controlled trials that compared the effectiveness of continuous isoniazid with 6 months of isoniazid. Outcomes of interest were TB incidence, mortality, adverse events and risk of drug resistance. Data were pooled using fixed-effects meta-analysis.
Three studies were included, from Botswana, South Africa and India. The risk of active TB was 38% lower among patients receiving continuous isoniazid compared with isoniazid regimen for 6 months [relative risk (RR) 0.62, 95% confidence interval (CI): 0.42-0.89; I = 0%], and 49% lower for those with a positive tuberculin skin test (TST) (RR 0.51, 95% CI: 0.30-0.86; I = 7%). Similarly, individuals with positive TST had a 50% lower chance of death (RR 0.50, 95% CI: 0.27-0.91; I = 3%). Two studies found no evidence of an increase in adverse events in the continuous isoniazid group, whereas a third study, that used a different definition for adverse events, found strong evidence of increase. There was no evidence of increased drug resistance when continuous isoniazid was given.
For PLHIV in settings with high TB and HIV prevalence and transmission, continuous isoniazid for at least 36 months is beneficial and probably outweighs the risk of increased adverse events compared with an isoniazid regimen for 6 months
PASS to End TB in Europe: Accelerated efforts on prevention and systematic screening to end tuberculosis in the WHO European Region by 2030
No full textObjectives: Outline the objectives, methods, and initial stages of the Prevention and Systematic Screening (PASS) initiative, a complimentary element of the innovative new approach of technical assistance mechanisms of WHO and its partners to countries aligned to the Regional TB Action Plan to End TB in the European Region by 2030. Design: To provide an objective and critical overview of the existing landscape on TB epidemic in the WHO European Region (the European Region) and ii) identify the strategic significance of proactive measures aimed at approaching TB pre-elimination in the Region. Results: Interventions primarily include systematic screening for TB disease and treatment for TB infection (TBI). Conclusions: PASS to End TB is an exemplary initiative of how technical and funding partners are joining hands to support national health programmes to work towards global commitments to curb major public health challenges like TB
Co-receptor CD8-mediated modulation of T-cell receptor functional sensitivity and epitope recognition degeneracy
No full textThe interaction between T-cell receptors (TCRs) and peptide epitopes is highly degenerate: a TCR is capable of interacting productively with a wide range of different peptide ligands, involving not only cross-reactivity proper (similar epitopes elicit strong responses), but also polyspecificity (ligands with distinct physicochemical properties are capable of interacting with the TCR). Degeneracy does not gainsay the fact that TCR recognition is fundamentally specific: for the vast majority of ligands, the functional sensitivity of a given TCR is virtually null whereas this TCR has an appreciable functional sensitivity only for a minute fraction of all possible ligands. Degeneracy can be described mathematically as the probability that the functional sensitivity, of a given TCR to a randomly selected ligand, exceeds a set value. Variation of this value generates a statistical distribution that characterizes TCR degeneracy. This distribution can be modeled on the basis of a Gaussian distribution for the TCR/ligand dissociation energy. The kinetics of the TCR and the MHCI molecule can be used to transform this underlying Gaussian distribution into the observed distribution of functional sensitivity values. In the present paper, the model is extended by accounting explicitly for the kinetics of the interaction between the co-receptor and the MHCI molecule. We show that T-cells can modulate the level of degeneracy by varying the density of co-receptors on the cell surface. This could allow for an analog of avidity maturation during incipient T-cell responses
Optimizing the cascade of prevention to protect people from tuberculosis: A potential game changer for reducing global tuberculosis incidence
No full text: The provision of tuberculosis preventive treatment is one of the critical interventions to reduce tuberculosis incidence and ultimately eliminate the disease, yet we still miss appropriate tools for an impactful intervention and treatment coverage remains low. We used recent data, epidemiological estimates, and research findings to analyze the challenges of each step of the cascade of tuberculosis prevention that currently delay the strategy implementation. We addressed research gaps and implementation bottlenecks that withhold key actions in tuberculosis case finding, testing for tuberculosis infection, provision of preventive treatment with safer, shorter regimens and supporting people to complete their treatment. Empowering communities to generate demand for preventive therapy and other prevention services in a holistic manner and providing adequate financial support to sustain implementation are essential requirements. The adoption of an effective, universal monitoring and evaluation system is a prerequisite to provide general and granular insight, and to steer progress of the tuberculosis infection strategy at global and local level
Queer Encounters in the Archive: Misplaced Love Letters and Autobiographical Homes
No full textThe chapter contains a report of the ongoing research into queer voices and architecture at the Nieuwe Instituut in Rotterdam, which holds the National Collection of Dutch Architecture and Urban Planning. After introducing the National Collection, the authors critically examine how its internal power dynamics and mechanisms privilege certain voices while marginalizing others, followed by a brief overview of earlier ‘queering’ initiatives. In the second part of this chapter, the authors present a selection from the National Collection of three post-war architects who resisted the sexual norms and expectations of their times: Onno Greiner, Dick van Woerkom and Wim den Boon. Their incomplete histories are told through the traces of queer desires and lifestyles which haunt their archives. By discussing their autobiographical house designs, the authors aim to foreground practices of queer worldmaking in the National Collection that let us imagine queer ways of inhabiting, dwelling, and living, while reassessing the history of Dutch modern architecture and some of its tenets related to transparancy, spatial concepts and interior design.Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Space & Typ
Playscapes: Creating Space for Young Children's Physical Activity and Play
No full textYoung children often lack opportunities to play in a physically active way. This is particularly the case for children with cancer and other chronic diseases, who regularly undergo periods of hospitalization. Promoting their physical activity and play can contribute to their health, wellbeing, and development. This thesis develops ‘Playscapes’ – a design perspective that emphasizes the unstructured and spontaneous nature of young children’s physical activity. Playscapes encourages designers to enable such physical activity through the design of open-ended and ambiguous playthings. By designing such playthings for children with cancer, this thesis contributes to turning hospital environments, such as patient rooms and waiting areas, into potential ‘landscapes for physical activity and play’.Human Information Communication DesignDesign Aesthetic
Bench marking AmpliDiff for Human Monkeypox, Hiv-1 and Influenza-A
No full textAmpliDiff provides a method which takes a list of genomes and their lineages, and finds a set of amplicons and their primers in such a way that these amplicons can be used to differentiate between the lineages of a specific virus. While it has been shown that AmpliDiff find results comparable to whole genome sequencing for SARS-CoV-2 when looking at abundance estimations, it is not know how well it performs for other viruses, or what factors of a virus impacts the performance of the amplicons found by AmpliDiff.\\In this paper we will be showing the effectiveness of AmpliDiff on Human monkeypox, HIV-1 and Influenza-A. By running AmpliDiff for the three viruses mentioned above, we obtain sets of amplicons, which are used to do a lineage abundance estimation. By then comparing the estimation to the know abundance we calculate the Mean Average Error (MAE). This MAE will then be used to compare against the MAE obtained from doing a abundance estimation based on whole genome sequencing. By comparing the amplicons against whole genome sequencing (wgs), we show that using viruses with longer genomes positively impacts the performance of the amplicons. We also show that the amount of misalignment characters added by the Multiple Sequence Alignemnt (MSA), impacts the required settings for AmpliDiff to find amplicons, and can negatively impact the MAE.Finally, we show that AmpliDiff can be run, with some minor changes to the code base, on segmented genomes, with performance similar to that of single segment genomes.CSE3000 Research ProjectComputer Science and Engineerin
Framework for the evaluation of new tests for tuberculosis infection
No full textThe scale-up of tuberculosis (TB) preventive treatment (TPT) must be accelerated to achieve the targets set by the United Nations High-level Meeting on TB and the End TB Strategy. The scale-up of effective TPT is hampered by concerns about operational challenges to implement the existing tests for TB infection. New simpler tests could facilitate the scale-up of testing for TB infection. We present a framework for evaluation of new immunodiagnostic tests for the detection of TB infection, with an aim to facilitate their standardised evaluation and accelerate adoption into global and national policies and subsequent scale-up. The framework describes the principles to be considered when evaluating new tests for TB infection and provides guidance to manufacturers, researchers, regulators and other users on study designs, populations, reference standards, sample size calculation and data analysis and it is also aligned with the Global Strategy for TB Research and Innovation adopted by the World Health Assembly in 2020. We also briefly describe technical issues that should be considered when evaluating new tests, including the safety for skin tests, costs incurred by patients and the health system patient, and operational characteristics
Creating a Framework for Effective Innovation Project Portfolio Management
No full textMost firms have more ideas for innovation projects than the R&D budget can support. On top of that, the industry of firm-X (at which the research took place) is characterized with long development cycles and expensive full scale testing. Therefore, it takes these firms a long time to actually see effects in form of the returns on their investments. Selecting the right innovation projects becomes very important for the long term survival of these firms. Innovation Project Portfolio Management (IPPM) has the potential to bring considerable benefits to structure the Innovation Project Portfolio (IPP) of these organizations, being a mindset where portfolio thinking is central. However many tools used for IPPM are based upon unreliable information or implicit judgment reducing the effectiveness. The design of an integrated and effective IPPM framework and understanding the factors that affect this framework are central in this research. This thesis describes the design of such an IPPM framework for the industry of firm-X, which is based on firm-X. It has been investigated at firm-X how the following aspects affect the IPPM decision making process: long term, top-down/bottom-up innovation approach, technological push & pull, formality of IPPM approach, and inter-organizational innovation activities. These aspects are important because they are affected by the choices made in the IPPM decision making process. Especially the collaboration of inter-organizational innovation activities can increase the value of R&D and also increase the performance of the current IPP. To conduct this research first of all a literature study was undertaken to understand the concepts related to IPPM and investigate contemporary tools for IPPM. Next, the current framework at firm-X is assessed by analyzing internal documents and conducting open interviews. Thirdly semi-structured interviews have been executed in two rounds with respectively 13 and 5 respondents from firm-X to find out how the aspects central in this study affect the IPPM decision making process. Finally, the results of the preceding are used to design an integrated and effective IPPM framework. The results show that top down/bottom-up innovation approach, a long term focus, and technology push & pull can be integrated in the framework. The interviews show in contrast to the theory that not all innovation projects should be aligned with the strategy, in particular innovation projects that are radical and young need to be given space to develop. The reason why this is done, is because it is often difficult to assess whether these innovation projects fit the strategy. The literature study and the research conducted at firm-X leads to a set of requirements for the new framework. The general framework consists of four steps, 1) measuring the current IPP state, 2) indicating the desired IPP state, 3) comparing the two states, 4) use the outcome of step three to adjust the current IPP state to approach the desired IPP state. This framework will help to reduce implicit judgment in the decision making process and will create a more systematic approach to select the right innovation projects. This integrated approach should lead to achieving the three goals of effective IPPM: strategy alignment, value maximization and creating balance IPP. The four steps of the general framework just discussed are transformed into a framework that is applicable at firm-X is based on a strategic bucket approach, technology roadmapping, and expected commercial value (ECV) calculations. Traditionally the strategic bucket approach is used to divide the R&D budget over one set of buckets. In the new framework the strategic bucket approach is operationalized by dividing R&D over multiple sets of buckets. This is done by dividing the R&D budget over four sets characteristics of innovation: 1) Technology Readiness Levels (TRL’s), 2) parts of the value chain, 3) product groups and 4) key technologies. These four characteristics lead to four sets of independent strategic buckets that indicate the current IPP state. The desired state of the R&D budget over the different TRL’s and parts of the value chain were indicated in interviews (with firm-X employees), therefore allowing an easy comparison of the current and the desired IPP state. The desired state of the Product Groups (PG) and Key Technologies (KT) is dependent on both the business environment and strategy. An ECV calculation of all the future products (indicated in the technology roadmap) will indicate the importance of each PG and KT for the future of firm-X, which can be seen as an indication of the desired state for the PG and KT. This approach enables that the four innovation characteristics of the framework can be balanced at the same time. Also, technology roadmaps that show development logic limit the number of IPP combinations. The aforementioned method in turn helps in choosing a specific path for selection of innovation projects that match the four desired states of TRL, parts of the value chain, PG and KT. It is due to these characteristics that the effect of inter-organizational innovation activities can easily be incorporated to see its effect on the current IPP state. Finally during the thesis also the supporting tools have been developed for the framework, meaning that an excel basis has been developed where all the innovation projects can be summarized and then automatically the graphs of the four characteristics for the current and desired IPP state are created. Also a program has been written in the matlab environment that can read the excel file and then produces the technology roadmaps. In this way the new IPPM framework can be supported, increasing the speed and the creation of the evidence based decision making process in IPPM.Management of TechnologyStrategy, Technology & EntrepreneurshipTechnology, Policy and Managemen
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