Characterisation of the Leukemic Stem Cell in a Murine Model of CALM/AF10 Positive Myeloid Leukemia

We have demonstrated, that an acute leukemia with a predominantly myeloid phenotype can be propagated by a progenitor with lymphoid characteristics in a mouse model of the t(10;11) (p13;q14) translocation. Mice transplanted with bone marrow retrovirally engineered to express the leukemia specific CALM/AF10 fusion gene consistently developed an acute leukemia with a short latency. The leukemia showed characteristic myeloid features such as the presence of myeloid marker positive cells infiltrating multiple hematopoietic and non-hematopoietic organs, the positivity of blasts for myeloid specific histochemical stainings and the depletion of the lymphoid compartment in lymphoid organs. Apart from the major population of cells expressing myeloid but not lymphoid markers (M population), a smaller population of cells expressing myeloid markers as well as the lymphoid marker B220 ( B/M population) and a smaller population expressing only the B220 marker (B population) could be detected in all mice. We determined that the frequency of leukemia propagating cells was the highest in the B population and that this population could give rise to the other two populations of cells, namely the B/M and the M populations. This indicated that the leukemic stem cell candidate for the myeloid leukemia in this model of CALM/AF10 induced transformation is a B220 + cell. Further characterization of these candidate LSCs revealed the presence of D-JH rearrangements and the absence of Pax5 transcription. These cells were characterised as being CD43 + /AA4.1 + /HSA low-pos/CD19 -/FLT3R + /IL-7R low-neg c-kit low-neg and expressing the early B cell factor (EBF) transcripts as well as transcripts for the myeloperoxidase (MPO) gene,bearing a resemblance to Pax5 knockout preBI cells. These findings indicate that the leukemia-propagating cell in a subset of acute myeloid leukemias could be a cell with lymphoid characteristics. The fact that this progenitor cell expressed markers different from those expressed by the bulk leukemic population but could still propagate the leukemia raises the interesting possibility of selectively targeting these cells using novel therapeutic strategies that aim to eliminate these LSCs

Mapping geographical inequalities in access to drinking water and sanitation facilities in low-income and middle-income countries, 2000-17

BACKGROUND: Universal access to safe drinking water and sanitation facilities is an essential human right, recognised in the Sustainable Development Goals as crucial for preventing disease and improving human wellbeing. Comprehensive, high-resolution estimates are important to inform progress towards achieving this goal. We aimed to produce high-resolution geospatial estimates of access to drinking water and sanitation facilities. METHODS: We used a Bayesian geostatistical model and data from 600 sources across more than 88 low-income and middle-income countries (LMICs) to estimate access to drinking water and sanitation facilities on continuous continent-wide surfaces from 2000 to 2017, and aggregated results to policy-relevant administrative units. We estimated mutually exclusive and collectively exhaustive subcategories of facilities for drinking water (piped water on or off premises, other improved facilities, unimproved, and surface water) and sanitation facilities (septic or sewer sanitation, other improved, unimproved, and open defecation) with use of ordinal regression. We also estimated the number of diarrhoeal deaths in children younger than 5 years attributed to unsafe facilities and estimated deaths that were averted by increased access to safe facilities in 2017, and analysed geographical inequality in access within LMICs. FINDINGS: Across LMICs, access to both piped water and improved water overall increased between 2000 and 2017, with progress varying spatially. For piped water, the safest water facility type, access increased from 40·0% (95% uncertainty interval [UI] 39·4-40·7) to 50·3% (50·0-50·5), but was lowest in sub-Saharan Africa, where access to piped water was mostly concentrated in urban centres. Access to both sewer or septic sanitation and improved sanitation overall also increased across all LMICs during the study period. For sewer or septic sanitation, access was 46·3% (95% UI 46·1-46·5) in 2017, compared with 28·7% (28·5-29·0) in 2000. Although some units improved access to the safest drinking water or sanitation facilities since 2000, a large absolute number of people continued to not have access in several units with high access to such facilities (>80%) in 2017. More than 253 000 people did not have access to sewer or septic sanitation facilities in the city of Harare, Zimbabwe, despite 88·6% (95% UI 87·2-89·7) access overall. Many units were able to transition from the least safe facilities in 2000 to safe facilities by 2017; for units in which populations primarily practised open defecation in 2000, 686 (95% UI 664-711) of the 1830 (1797-1863) units transitioned to the use of improved sanitation. Geographical disparities in access to improved water across units decreased in 76·1% (95% UI 71·6-80·7) of countries from 2000 to 2017, and in 53·9% (50·6-59·6) of countries for access to improved sanitation, but remained evident subnationally in most countries in 2017. INTERPRETATION: Our estimates, combined with geospatial trends in diarrhoeal burden, identify where efforts to increase access to safe drinking water and sanitation facilities are most needed. By highlighting areas with successful approaches or in need of targeted interventions, our estimates can enable precision public health to effectively progress towards universal access to safe water and sanitation. FUNDING: Bill & Melinda Gates Foundation

Mapping geographical inequalities in childhood diarrhoeal morbidity and mortality in low-income and middle-income countries, 2000-17 : analysis for the global burden of disease study 2017

Background Across low-income and middle-income countries (LMICs), one in ten deaths in children younger than 5 years is attributable to diarrhoea. The substantial between-country variation in both diarrhoea incidence and mortality is attributable to interventions that protect children, prevent infection, and treat disease. Identifying subnational regions with the highest burden and mapping associated risk factors can aid in reducing preventable childhood diarrhoea. Methods We used Bayesian model-based geostatistics and a geolocated dataset comprising 15 072 746 children younger than 5 years from 466 surveys in 94 LMICs, in combination with findings of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017, to estimate posterior distributions of diarrhoea prevalence, incidence, and mortality from 2000 to 2017. From these data, we estimated the burden of diarrhoea at varying subnational levels (termed units) by spatially aggregating draws, and we investigated the drivers of subnational patterns by creating aggregated risk factor estimates. Findings The greatest declines in diarrhoeal mortality were seen in south and southeast Asia and South America, where 54·0% (95% uncertainty interval [UI] 38·1-65·8), 17·4% (7·7-28·4), and 59·5% (34·2-86·9) of units, respectively, recorded decreases in deaths from diarrhoea greater than 10%. Although children in much of Africa remain at high risk of death due to diarrhoea, regions with the most deaths were outside Africa, with the highest mortality units located in Pakistan. Indonesia showed the greatest within-country geographical inequality; some regions had mortality rates nearly four times the average country rate. Reductions in mortality were correlated to improvements in water, sanitation, and hygiene (WASH) or reductions in child growth failure (CGF). Similarly, most high-risk areas had poor WASH, high CGF, or low oral rehydration therapy coverage. Interpretation By co-analysing geospatial trends in diarrhoeal burden and its key risk factors, we could assess candidate drivers of subnational death reduction. Further, by doing a counterfactual analysis of the remaining disease burden using key risk factors, we identified potential intervention strategies for vulnerable populations. In view of the demands for limited resources in LMICs, accurately quantifying the burden of diarrhoea and its drivers is important for precision public health. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. ***Please note that there are multiple authors for this article therefore only the name of the first 5 including Federation University Australia affiliate “Muhammad Rahman” is provided in this record***C A T Antonio reports grants and personal fees from Johnson & Johnson (Philippines), outside the submitted work. S J Dunachie reports grants from The Fleming Fund at UK Department of Health & Social Care, during the conduct of the study. M Jakovljevic reports grants from Ministry of Education Science and Technological Development of The Republic of Serbia, outside the submitted work. J J J

Efficient Processing of Geospatial mHealth Data Using a Scalable Crowdsensing Platform

Smart sensors and smartphones are becoming increasingly prevalent. Both can be used to gather environmental data (e.g., noise). Importantly, these devices can be connected to each other as well as to the Internet to collect large amounts of sensor data, which leads to many new opportunities. In particular, mobile crowdsensing techniques can be used to capture phenomena of common interest. Especially valuable insights can be gained if the collected data are additionally related to the time and place of the measurements. However, many technical solutions still use monolithic backends that are not capable of processing crowdsensing data in a flexible, efficient, and scalable manner. In this work, an architectural design was conceived with the goal to manage geospatial data in challenging crowdsensing healthcare scenarios. It will be shown how the proposed approach can be used to provide users with an interactive map of environmental noise, allowing tinnitus patients and other health-conscious people to avoid locations with harmful sound levels. Technically, the shown approach combines cloud-native applications with Big Data and stream processing concepts. In general, the presented architectural design shall serve as a foundation to implement practical and scalable crowdsensing platforms for various healthcare scenarios beyond the addressed use case

Sudden sensorineural hearing loss:What can we learn from examining Reddit posts?

Background Many patients with sudden sensorineural hearing loss may seek hearing health information and social support online, although little is known about the online information seeking behaviour. Objective The present study aimed to examine the discussions around sudden sensorineural hearing loss in Reddit posts. Method A total of 526 Reddit posts about sudden sensorineural hearing loss were extracted and analysed using qualitative and quantitative methods. Results The content analysis identified eight main categories. Most of the posts were on topics of: sharing personal experiences (34 per cent), describing symptoms (31 per cent), discussing treatment options (36 per cent) and discussing possible causes (19 per cent) of sudden sensorineural hearing loss. The sudden sensorineural hearing loss Reddit posts varied significantly in terms of linguistic variables when compared to baseline Reddit posts. Reddit posts by individuals with sudden sensorineural hearing loss had significantly higher engagement, higher authenticity and made more references to their body when compared to other users. Conclusion The study results provide insights that can be helpful for professionals during clinical interactions

Design and Implementation of a Scalable Crowdsensing Platform for Geospatial Data of Tinnitus Patients

Smart devices and low-powered sensors are becoming increasingly ubiquitous and nowadays almost all of these devices are connected, which is a promising foundation for crowdsensing of data related to various environmental phenomena. Resulting data is especially meaningful when it is related to time and location. Interestingly, many existing approaches built their solution on monolithic backends that process data on a per-request basis. However, for many scenarios, such technical setting is not suitable for managing data requests of a large crowd. For example, when dealing with millions of data points, still many challenges arise for modern smartphones if calculations or advanced visualization features must be accomplished directly on the smartphone. Therefore, the work at hand proposes an architectural design for managing geospatial data of tinnitus patients, which combines a cloudnative approach with Big Data concepts used in the Internet of Things. The presented architectural design shall serve as a generic foundation to implement (1) a scalable backend for a platform that covers the aforementioned crowdsensing requirements as well as to provide (2) a sophisticated stream processing concept to calculate and pre-aggregate incoming measurement data of tinnitus patients. Following this, this paper presents a visualization feature to provide users with a comprehensive overview of noise levels in their environment based on noise measurements. This shall help tinnitus or hearing-impaired patients to avoid locations with a burdensome sound level

Mapping Geographical Inequalities in Access to Drinking Water and Sanitation Facilities in Low-Income and Middle-Income Countries, 2000–17

Background Universal access to safe drinking water and sanitation facilities is an essential human right, recognised in the Sustainable Development Goals as crucial for preventing disease and improving human wellbeing. Comprehensive, high-resolution estimates are important to inform progress towards achieving this goal. We aimed to produce high-resolution geospatial estimates of access to drinking water and sanitation facilities. Methods We used a Bayesian geostatistical model and data from 600 sources across more than 88 low-income and middle-income countries (LMICs) to estimate access to drinking water and sanitation facilities on continuous continent-wide surfaces from 2000 to 2017, and aggregated results to policy-relevant administrative units. We estimated mutually exclusive and collectively exhaustive subcategories of facilities for drinking water (piped water on or off premises, other improved facilities, unimproved, and surface water) and sanitation facilities (septic or sewer sanitation, other improved, unimproved, and open defecation) with use of ordinal regression. We also estimated the number of diarrhoeal deaths in children younger than 5 years attributed to unsafe facilities and estimated deaths that were averted by increased access to safe facilities in 2017, and analysed geographical inequality in access within LMICs. Findings Across LMICs, access to both piped water and improved water overall increased between 2000 and 2017, with progress varying spatially. For piped water, the safest water facility type, access increased from 40·0% (95% uncertainty interval [UI] 39·4–40·7) to 50·3% (50·0–50·5), but was lowest in sub-Saharan Africa, where access to piped water was mostly concentrated in urban centres. Access to both sewer or septic sanitation and improved sanitation overall also increased across all LMICs during the study period. For sewer or septic sanitation, access was 46·3% (95% UI 46·1–46·5) in 2017, compared with 28·7% (28·5–29·0) in 2000. Although some units improved access to the safest drinking water or sanitation facilities since 2000, a large absolute number of people continued to not have access in several units with high access to such facilities (\u3e80%) in 2017. More than 253 000 people did not have access to sewer or septic sanitation facilities in the city of Harare, Zimbabwe, despite 88·6% (95% UI 87·2–89·7) access overall. Many units were able to transition from the least safe facilities in 2000 to safe facilities by 2017; for units in which populations primarily practised open defecation in 2000, 686 (95% UI 664–711) of the 1830 (1797–1863) units transitioned to the use of improved sanitation. Geographical disparities in access to improved water across units decreased in 76·1% (95% UI 71·6–80·7) of countries from 2000 to 2017, and in 53·9% (50·6–59·6) of countries for access to improved sanitation, but remained evident subnationally in most countries in 2017. Interpretation Our estimates, combined with geospatial trends in diarrhoeal burden, identify where efforts to increase access to safe drinking water and sanitation facilities are most needed. By highlighting areas with successful approaches or in need of targeted interventions, our estimates can enable precision public health to effectively progress towards universal access to safe water and sanitation

The overlapping burden of the three leading causes of disability and death in sub-Saharan African children

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