1. |
- Khan, Md Kawsar, et al.
(författare)
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In silico predicted mycobacterial epitope elicits in vitro T-cell responses
- 2014
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Ingår i: Molecular Immunology. - : Elsevier BV. - 0161-5890 .- 1872-9142. ; 61:1, s. 16-22
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Tidskriftsartikel (refereegranskat)abstract
- Epitope-based vaccines permit the selection of only a specific subset of epitopes to induce the necessary immune response, thus providing a rational alternative to conventional design approaches. Using a range of immunoinformatics tools, we identified a novel, contiguous 28 amino acid multi-epitope cluster within the highly conserved secretory protein Ag85B of Mycobacterium tuberculosis, the causative agent of TB. This cluster, named Ep85B, is composed of epitopes which bind to three HLA Class I and 15 Class II molecules, and harbors the potential to generate 99% population coverage in TB-endemic regions. We experimentally evaluated the capacity of Ep85B to elicit T-cell immune responses using whole blood cells and, as predicted, observed significant increases in populations of both CD4+ and memory CD4+ CD45RO+ T-cells. Our results demonstrate the practical utility of an epitope-based design methodology - a strategy that, following further evaluation, may serve as an additional tool for the development of novel vaccine candidates against TB and other diseases.
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2. |
- Mazzola, Federico, et al.
(författare)
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The sub-band structure of atomically sharp dopant profiles in silicon
- 2020
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Ingår i: npj Quantum Materials. - : Springer Science and Business Media LLC. - 2397-4648. ; 5:1
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Tidskriftsartikel (refereegranskat)abstract
- The downscaling of silicon-based structures and proto-devices has now reached the single-atom scale, representing an important milestone for the development of a silicon-based quantum computer. One especially notable platform for atomic-scale device fabrication is the so-called Si:P δ-layer, consisting of an ultra-dense and sharp layer of dopants within a semiconductor host. Whilst several alternatives exist, it is on the Si:P platform that many quantum proto-devices have been successfully demonstrated. Motivated by this, both calculations and experiments have been dedicated to understanding the electronic structure of the Si:P δ-layer platform. In this work, we use high-resolution angle-resolved photoemission spectroscopy to reveal the structure of the electronic states which exist because of the high dopant density of the Si:P δ-layer. In contrast to published theoretical work, we resolve three distinct bands, the most occupied of which shows a large anisotropy and significant deviation from simple parabolic behaviour. We investigate the possible origins of this fine structure, and conclude that it is primarily a consequence of the dielectric constant being large (ca. double that of bulk Si). Incorporating this factor into tight-binding calculations leads to a major revision of band structure; specifically, the existence of a third band, the separation of the bands, and the departure from purely parabolic behaviour. This new understanding of the band structure has important implications for quantum proto-devices which are built on the Si:P δ-layer platform.
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3. |
- Peven, Kimberly, et al.
(författare)
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Stillbirths including intrapartum timing: EN-BIRTH multi-country validation study.
- 2021
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Ingår i: BMC pregnancy and childbirth. - : Springer Science and Business Media LLC. - 1471-2393. ; 21:Suppl 1
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Tidskriftsartikel (refereegranskat)abstract
- An estimated >2 million babies stillborn around the world each year lack visibility. Low- and middle-income countries carry 84% of the burden yet have the least data. Most births are now in facilities, hence routine register-recording presents an opportunity to improve counting of stillbirths, but research is limited, particularly regarding accuracy. This paper evaluates register-recorded measurement of hospital stillbirths, classification accuracy, and barriers and enablers to routine recording.The EN-BIRTH mixed-methods, observational study took place in five hospitals in Bangladesh, Nepal and Tanzania (2017-2018). Clinical observers collected time-stamped data on perinatal care and birth outcomes as gold standard. To assess accuracy of routine register-recorded stillbirth rates, we compared birth outcomes recorded in labour ward registers to observation data. We calculated absolute rate differences and individual-level validation metrics (sensitivity, specificity, percent agreement). We assessed misclassification of stillbirths with neonatal deaths. To examine stillbirth appearance (fresh/macerated) as a proxy for timing of death, we compared appearance to observed timing of intrauterine death based on heart rate at admission.23,072 births were observed including 550 stillbirths. Register-recorded completeness of birth outcomes was > 90%. The observed study stillbirth rate ranged from 3.8 (95%CI = 2.0,7.0) to 50.3 (95%CI = 43.6,58.0)/1000 total births and was under-estimated in routine registers by 1.1 to 7.3 /1000 total births (register: observed ratio 0.9-0.7). Specificity of register-recorded birth outcomes was > 99% and sensitivity varied between hospitals, ranging from 77.7-86.1%. Percent agreement between observer-assessed birth outcome and register-recorded birth outcome was very high across all hospitals and all modes of birth (> 98%). Fresh or macerated stillbirth appearance was a poor proxy for timing of stillbirth. While there were similar numbers of stillbirths misclassified as neonatal deaths (17/430) and neonatal deaths misclassified as stillbirths (21/36), neonatal deaths were proportionately more likely to be misclassified as stillbirths (58.3% vs 4.0%). Enablers to more accurate register-recording of birth outcome included supervision and data use.Our results show these routine registers accurately recorded stillbirths. Fresh/macerated appearance was a poor proxy for intrapartum stillbirths, hence more focus on measuring fetal heart rate is crucial to classification and importantly reduction in these preventable deaths.
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4. |
- Shamba, Donat, et al.
(författare)
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Barriers and enablers to routine register data collection for newborns and mothers: EN-BIRTH multi-country validation study.
- 2021
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Ingår i: BMC pregnancy and childbirth. - : Springer Science and Business Media LLC. - 1471-2393. ; 21:Suppl 1
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Tidskriftsartikel (refereegranskat)abstract
- Policymakers need regular high-quality coverage data on care around the time of birth to accelerate progress for ending preventable maternal and newborn deaths and stillbirths. With increasing facility births, routine Health Management Information System (HMIS) data have potential to track coverage. Identifying barriers and enablers faced by frontline health workers recording HMIS source data in registers is important to improve data for use.The EN-BIRTH study was a mixed-methods observational study in five hospitals in Bangladesh, Nepal and Tanzania to assess measurement validity for selected Every Newborn coverage indicators. We described data elements required in labour ward registers to track these indicators. To evaluate barriers and enablers for correct recording of data in registers, we designed three interview tools: a) semi-structured in-depth interview (IDI) guide b) semi-structured focus group discussion (FGD) guide, and c) checklist assessing care-to-documentation. We interviewed two groups of respondents (January 2018-March 2019): hospital nurse-midwives and doctors who fill ward registers after birth (n = 40 IDI and n = 5 FGD); and data collectors (n = 65). Qualitative data were analysed thematically by categorising pre-identified codes. Common emerging themes of barriers or enablers across all five hospitals were identified relating to three conceptual framework categories.Similar themes emerged as both barriers and enablers. First, register design was recognised as crucial, yet perceived as complex, and not always standardised for necessary data elements. Second, register filling was performed by over-stretched nurse-midwives with variable training, limited supervision, and availability of logistical resources. Documentation complexity across parallel documents was time-consuming and delayed because of low staff numbers. Complete data were valued more than correct data. Third, use of register data included clinical handover and monthly reporting, but little feedback was given from data users.Health workers invest major time recording register data for maternal and newborn core health indicators. Improving data quality requires standardised register designs streamlined to capture only necessary data elements. Consistent implementation processes are also needed. Two-way feedback between HMIS levels is critical to improve performance and accurately track progress towards agreed health goals.
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5. |
- Sinha, Rajib
(författare)
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Systems Modeling Approaches to Physical Resource Management : An Industrial Ecology Perspective
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Many of the present problems that we are facing arise as unanticipated side-effects of our own actions. Moreover, the solutions implemented to solve important problems often create new problems. To avoid unintended consequences, understanding complex systems is essential in devising policy instruments and in improving environmental management. Thus, this thesis investigated systems modeling approaches to under- stand complex systems and monitor the environmental performance of management actions. The overall aim of the work was to investigate the usefulness of different systems modeling approaches in supporting environmental management. A driver- based, pressure-oriented approach was adopted to investigate systems modeling tools. Material/substance flow analysis, environmental footprinting, input-output analysis, process-based dynamic modeling, and systems dynamics modeling approaches were applied in different cases to investigate strengths and weaknesses of the tools in generating an understanding of complex systems. Three modeling and accounting approaches were also tested at different systems scales to support environmental mon- itoring. Static modeling approaches were identified as fundamental to map, account, and monitor physical resource metabolism in production and consumption systems, whereas dynamic modeling showed strengths in understanding complex systems. The results suggested that dynamic modeling approaches should be conducted on top of static analysis to understand the complexity of systems when devising and testing policy instruments. To achieve proactive monitoring, a pressure-based assessment was proposed instead of the mainstream impact/state-based approach. It was also concluded that the LCA community should shift the focus of its assessments to pressures instead of impacts.
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