Household water use and greywater management in Khulna city, Bangladesh.

While substantial progress has been made in improving water and sanitation services in low- and middle-income countries, aligned basic services such as greywater, stormwater, and solid waste management have progressed little in recent decades. Data was collected in Khulna city, Bangladesh via a household survey (n = 192) of low-income areas exploring domestic water use and greywater volumes, characteristics, and disposal practices. Most households (71%) use a piped water supply for domestic purposes, supplemented by seasonal rainwater harvesting (26%) and greywater use (13%). Of the total water used by households (mean: 594 L/household/day and equivalent to 116 L/person/day), approximately 58% becomes greywater through bathing, dishwashing, religious practices, handwashing, laundry, and mopping. Greywater produced ranges from 61-1274 L/household/day, with a mean of 345 L/household/day and equivalent to 78.4 L/person/day. Greywater characteristics vary depending on the activity, individual behaviours and any products used during cooking, bathing, or cleaning. After generation, households dispose greywater to open drains (67%), nearby waterbodies (17%) directly to the ground (9%), or decentralised wastewater treatment system (7%). Without services for greywater management, greywater disposal may have considerable public and environmental health implications, necessitating careful attention and oversight from service-providers and stakeholders beyond the household-level.

Nuclear Vav3 is required for polycomb repression complex-1 activity in B-cell lymphoblastic leukemogenesis.

Acute B-cell lymphoblastic leukemia (B-ALL) results from oligo-clonal evolution of B-cell progenitors endowed with initiating and propagating leukemia properties. The activation of both the Rac guanine nucleotide exchange factor (Rac GEF) Vav3 and Rac GTPases is required for leukemogenesis mediated by the oncogenic fusion protein BCR-ABL. Vav3 expression becomes predominantly nuclear upon expression of BCR-ABL signature. In the nucleus, Vav3 interacts with BCR-ABL, Rac, and the polycomb repression complex (PRC) proteins Bmi1, Ring1b and Ezh2. The GEF activity of Vav3 is required for the proliferation, Bmi1-dependent B-cell progenitor self-renewal, nuclear Rac activation, protein interaction with Bmi1, mono-ubiquitination of H2A(K119) (H2AK119Ub) and repression of PRC-1 (PRC1) downstream target loci, of leukemic B-cell progenitors. Vav3 deficiency results in de-repression of negative regulators of cell proliferation and repression of oncogenic transcriptional factors. Mechanistically, we show that Vav3 prevents the Phlpp2-sensitive and Akt (S473)-dependent phosphorylation of Bmi1 on the regulatory residue S314 that, in turn, promotes the transcriptional factor reprogramming of leukemic B-cell progenitors. These results highlight the importance of non-canonical nuclear Rho GTPase signaling in leukemogenesis.

MRI Patterns in Pediatric CNS Hemophagocytic Lymphohistiocytosis.

BACKGROUND AND PURPOSE: Neuroimaging has an important role in detecting CNS involvement in children with systemic or CNS isolated hemophagocytic lymphohistiocytosis. We characterized a cohort of pediatric patients with CNS hemophagocytic lymphohistiocytosis focusing on neuroradiologic features and assessed whether distinct MR imaging patterns and genotype correlations can be recognized. MATERIALS AND METHODS: We retrospectively enrolled consecutive pediatric patients diagnosed with hemophagocytic lymphohistiocytosis with CNS involvement treated at 2 pediatric neurology centers between 2010 and 2018. Clinical and MR imaging data were analyzed. RESULTS: Fifty-seven children (40 primary, 70%) with a median age of 36 months (interquartile range, 5.5-80.8 months) were included. One hundred twenty-three MR imaging studies were assessed, and 2 broad imaging patterns were identified. Pattern 1 (significant parenchymal disease, 32/57, 56%) was seen in older children (P = .004) with worse clinical profiles. It had 3 onset subpatterns: multifocal white matter lesions (21/32, 66%), brainstem predominant disease (5, 15%), and cerebellitis (6, 19%). All patients with the brainstem pattern failed to meet the radiologic criteria for chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids. An attenuated imaging phenotype (pattern 2) was seen in 25 patients (44%, 30 studies) and was associated with younger age. CONCLUSIONS: Distinct MR imaging patterns correlating with clinical phenotypes and possible genetic underpinnings were recognized in this cohort of pediatric CNS hemophagocytic lymphohistiocytosis. Disruptive mutations and missense mutations with absent protein expression correlate with a younger onset age. Children with brainstem and cerebellitis patterns and a negative etiologic work-up require directed assessment for CNS hemophagocytic lymphohistiocytosis.

Climate adaptation for rural water and sanitation systems in the Solomon Islands: A community scale systems model for decision support.

Delivering water and sanitation services are challenging in data poor rural settings in developing countries. In this paper we develop a Bayesian Belief Network model that supports decision making to increase the availability of safe drinking water in five flood-prone rural communities in the Solomon Islands. We collected quantitative household survey data and qualitative cultural and environmental knowledge through community focus group discussions. We combined these data to develop our model, which simulates the state of eight water sources and ten sanitation types and how they are affected by season and extreme events. We identify how climate and current practices can threaten the availability of drinking water for remote communities. Modelling of climate and intervention scenarios indicate that water security could be best enhanced through increased rainwater harvesting (assuming proper installation and maintenance). These findings highlight how a systems model can identify links between and improve understanding of water and sanitation, community behaviour, and the impacts of extreme events. The resultant BBN provides a tool for decision support to enhance opportunities for climate resilient water and sanitation service provision.

Water safety plans for water supply utilities in China, Cuba, France, Morocco and Spain: costs, benefits, and enabling environment elements.

Water Safety Plans (WSPs) are a management tool to identify and prioritize risks and implement appropriate control measures throughout the water supply chain, from catchment to consumer. WSPs have been implemented in over 90 countries; yet, costs, benefits and the enabling environment elements necessary for WSP implementation are under-studied. To better understand these factors, we conducted interviews with WSP implementation management teams from 20 private urban water utilities in China, Cuba, France, Morocco and Spain in 2014. Collectively, these utilities serve 10.6 million consumers and supply over 2.2 million m3/day of water to consumers. Time for WSP implementation to achieve certification averaged 13 months. The main startup cost was staff time, averaging 16.2 full-time equivalent person-months. Additional costs, averaging €16,777, were for training staff, hiring consultants, purchasing equipment, and certifying WSPs. Benefits commonly reported included improved hazard control, treatment practices, record keeping, and client and health agency confidence.

The implementation of environmental health policies in health care facilities: The case of Malawi.

Establishing and maintaining safe and sufficient environmental health (EH) conditions in health care facilities (HCFs) is important to prevent and control infections. In 2018, the Government of Malawi finalized an environmental health policy that defines specific targets and programs for EH in healthcare settings. This and other related policies have been used since 2010 as a guide for EH practice in HCFs, but the implementation of these policies has been incomplete to-date. This study qualitatively examines the successes and shortcomings of implementing these policies in Malawi's public HCFs. Thematic analysis of interviews with 53 respondents from all levels of government was used to identify the successes of the policies and the barriers to effective implementation using Contextual Interaction Theory. The greatest identified strength lies in the design of the EH department and its ability to connect individual HCFs and EH actors directly to the policy-making level of government. Identified barriers to implementation include: insufficient financial support; lack of human resources; incomplete reporting; poor stakeholder coordination; and insufficient training of EH actors. We recommend refresher trainings for all EH actors, the establishment of a directorate level EH position, and strengthened coordination to improve the collection, analysis, and reporting of monitoring data to enable EH actors to advocate for the additional funding needed to develop programs for EH personnel and to apply effective EH interventions.

Pro-poor governance in water and sanitation service delivery: evidence from Global Analysis and Assessment of Sanitation and Drinking Water surveys.

AIMS: The Sustainable Development Goal (SDG) for water and sanitation seeks to achieve universal and equitable access to safe and affordable drinking water and access to adequate and equitable sanitation and hygiene. This article examines what governments are doing to achieve this, paying particular attention to actions that governments report taking to better serve the poor and other vulnerable populations (i.e. pro-poor governance). This article also assesses the extent to which, and how, UN-Water's Global Analysis and Assessment of Sanitation and Drinking Water (GLAAS) has tracked governments' efforts to reach the poor since the inception of this global monitoring effort. METHOD: This article employs qualitative document analysis and iterative coding to identify pro-poor governance themes examined in GLAAS reports from 2008 to 2016 and provides a quantitative summary of findings related to pro-poor governance from the most recent GLAAS surveys. RESULTS: The dimensions of pro-poor governance and number of questions related to pro-poor governance in GLAAS surveys have increased from 2008 to 2016. While the majority of countries report taking actions to promote equity, many countries did not provide information about specific actions they were taking to provide better services to the poor. Moreover, several actions countries reported taking (e.g. implementing an increasing block tariff) are likely to be ineffective. CONCLUSION: The findings of this study raise concerns about the extent to which governments are taking - or are positioned to take - effective action to meet the SDG aspiration of safe and affordable water and sanitation services for all. Without information on what countries are doing to promote equity, policy makers and researchers are unable to discern which policies are effective in different contexts.

Assessing operational performance benefits of a Water Safety Plan implemented in Southwestern France.

AIMS: The World Health Organization (WHO) has recommended Water Safety Plans (WSPs) since 2004 as a means to reduce drinking water contamination and risks to human health. These risk management programs have shown promise across several potential areas of evaluation, such as economic benefits and regulatory compliance. Since WSPs are largely carried out by people who interact with water treatment equipment and processes, operational performance indicators may be key to understanding the mechanisms behind desirable WSP impacts such as water quality and public health improvement. METHOD: This study reports performance measures collected at a WSP implementation location in southwestern France over several years. RESULTS: Quantitative assessment of performance measures supported qualitative reports from utility managers. Results indicate significantly reduced duration of low-chlorine events at one production facility and a significant decrease in customer complaints related to water quality, manifesting reported improvements in operational performance and the customer service culture. CONCLUSION: The findings demonstrate some success stories and potential areas of future performance tracking. Cyclical iteration of the WSP can help to achieve continuous quality improvement. Successfully applied evaluation criteria such as the number of water quality complaints or alarm resolution time might be useful across other locations.

Targeting acute myeloid leukemia by drug-induced c-MYB degradation.

Despite advances in our understanding of the molecular basis for particular subtypes of acute myeloid leukemia (AML), effective therapy remains a challenge for many individuals suffering from this disease. A significant proportion of both pediatric and adult AML patients cannot be cured and since the upper limits of chemotherapy intensification have been reached, there is an urgent need for novel therapeutic approaches. The transcription factor c-MYB has been shown to play a central role in the development and progression of AML driven by several different oncogenes, including mixed lineage leukemia (MLL)-fusion genes. Here, we have used a c-MYB gene expression signature from MLL-rearranged AML to probe the Connectivity Map database and identified mebendazole as a c-MYB targeting drug. Mebendazole induces c-MYB degradation via the proteasome by interfering with the heat shock protein 70 (HSP70) chaperone system. Transient exposure to mebendazole is sufficient to inhibit colony formation by AML cells, but not normal cord blood-derived cells. Furthermore, mebendazole is effective at impairing AML progression in vivo in mouse xenotransplantation experiments. In the context of widespread human use of mebendazole, our data indicate that mebendazole-induced c-MYB degradation represents a safe and novel therapeutic approach for AML.

Sanitation marketing: A systematic review and theoretical critique using the capability approach.

Sanitation is a human right that benefits health. As such, technical and behavioural interventions are widely implemented to increase the number of people using sanitation facilities. These include sanitation marketing interventions (SMIs), in which external support agencies (ESAs) use a hybrid of commercial and social marketing tools to increase supply of, and demand for, sanitation products and services. However, there is little critical discourse on SMIs, or independent rigorous analysis on whether they increase or reduce well-being. Most available information is from ESAs about their own SMI implementation. We systematically reviewed the grey and peer-reviewed literature on sanitation marketing, including qualitatively analysing and calculating descriptive statistics for the parameters measured, or intended to be measured, in publications reporting on 33 SMIs. Guided by the capability approach to development we identified that publications for most SMIs (n = 31, 94%) reported on commodities, whilst fewer reported on parameters related to impacts on well-being (i.e., functionings, n = 22, 67%, and capabilities, n = 20, 61%). When evaluating future SMIs, it may be useful to develop a list of contextualised well-being indicators for the particular SMI's location, taking into account local cultural norms, with this list ideally co-produced with local stakeholders. We identified two common practices in SMIs that can reduce well-being and widen well-being inequalities; namely, the promotion of conspicuous consumption and assaults on dignity, and we discuss the mechanisms by which such impacts occur. We recommend that ESAs understand sanitation marketing's potential to reduce well-being and design SMIs to minimize such detrimental impacts. Throughout the implementation phase ESAs should continuously monitor for well-being impacts and adapt practices to optimise well-being outcomes for all involved.

Improving community health through marketing exchanges: A participatory action research study on water, sanitation, and hygiene in three Melanesian countries.

Diseases related to poor water, sanitation and hygiene (WaSH) are major causes of mortality and morbidity. While pursuing marketing approaches to WaSH to improve health outcomes is often narrowly associated with monetary exchange, marketing theory recognises four broad marketing exchange archetypes: market-based, non-market-based, command-based and culturally determined. This diversity reflects the need for parameters broader than monetary exchange when improving WaSH. This study applied a participatory action research process to investigate how impoverished communities in Melanesian urban and peri-urban informal settlements attempt to meet their WaSH needs through marketing exchange. Exchanges of all four archetypes were present, often in combination. Motivations for participating in the marketing exchanges were based on social relationships alongside WaSH needs, health aspirations and financial circumstances. By leveraging these motivations and pre-existing, self-determined marketing exchanges, WaSH practitioners may be able to foster WaSH marketing exchanges consistent with local context and capabilities, in turn improving community physical, mental and social health.

Eye on the B-ALL: B-cell receptor repertoires reveal persistence of numerous B-lymphoblastic leukemia subclones from diagnosis to relapse.

The strongest predictor of relapse in B-cell acute lymphoblastic leukemia (B-ALL) is the level of persistence of tumor cells after initial therapy. The high mutation rate of the B-cell receptor (BCR) locus allows high-resolution tracking of the architecture, evolution and clonal dynamics of B-ALL. Using longitudinal BCR repertoire sequencing, we find that the BCR undergoes an unexpectedly high level of clonal diversification in B-ALL cells through both somatic hypermutation and secondary rearrangements, which can be used for tracking the subclonal composition of the disease and detect minimal residual disease with unprecedented sensitivity. We go on to investigate clonal dynamics of B-ALL using BCR phylogenetic analyses of paired diagnosis-relapse samples and find that large numbers of small leukemic subclones present at diagnosis re-emerge at relapse alongside a dominant clone. Our findings suggest that in all informative relapsed patients, the survival of large numbers of clonogenic cells beyond initial chemotherapy is a surrogate for inherent partial chemoresistance or inadequate therapy, providing an increased opportunity for subsequent emergence of fully resistant clones. These results frame early cytoreduction as an important determinant of long-term outcome.

Rural:urban inequalities in post 2015 targets and indicators for drinking-water.

Disparities in access to drinking water between rural and urban areas are pronounced. Although use of improved sources has increased more rapidly in rural areas, rising from 62% in 1990 to 81% in 2011, the proportion of the rural population using an improved water source remains substantially lower than in urban areas. Inequalities in coverage are compounded by disparities in other aspects of water service. Not all improved sources are safe and evidence from a systematic review demonstrates that water is more likely to contain detectable fecal indicator bacteria in rural areas. Piped water on premises is a service enjoyed primarily by those living in urban areas so differentiating amongst improved sources would exacerbate rural:urban disparities yet further. We argue that an urban bias may have resulted due to apparent stagnation in urban coverage and the inequity observed between urban and peri-urban areas. The apparent stagnation at around 95% coverage in urban areas stems in part from relative population growth - over the last two decades more people gained access to improved water in urban areas. There are calls for setting higher standards in urban areas which would exacerbate the already extreme rural disadvantage. Instead of setting different targets, health, economic, and human rights perspectives, We suggest that the focus should be kept on achieving universal access to safe water (primarily in rural areas) while monitoring progress towards higher service levels, including greater water safety (both in rural and urban areas and among different economic strata).

Icelandic experience with water safety plans.

The aim of this study was to investigate accumulated experience with water safety plans in one of the first countries to adopt systematic preventive management for drinking-water safety. Water utilities in Iceland have had a legal obligation since 1995 to implement a systematic preventive approach to secure safety of drinking water and protect public health. The water utilities responded by implementing either an adapted HACCP (Hazard Analysis Critical Control Points) model for larger water utilities or a simpler five step model for smaller water utilities. The research was carried out at 16 water utilities that serve about two-thirds of the population of Iceland. Both qualitative and quantitative methods were used with the aim of analysing if and what benefits water safety plans bring for water utilities and what is needed for successful implementation and operation of such systems. The results of the study show that numerous benefits and even the process of going through the implementing process were considered to be of advantage and change the attitude of the staff and the utility culture. Some obstacles and shortcomings came to light, such as lack of documentation and lack of regular internal and external audit. There was little communication with the public, although some mentioned that good public relations are important to succeed with water safety plans. Many important elements of success were revealed of which intensive training of staff and participation of staff in the whole process are deemed the most important. It is also important to have simple and well-structured guidelines, and good cooperation with the health authorities.

Diagnostic difficulties in the management of H-type tracheoesophageal fistula.

PURPOSE: To evaluate the diagnostic difficulties and pitfalls in establishing the diagnosis of congenital H-type tracheoesophageal fistula. MATERIAL AND METHODS: A retrospective review of all cases of H-type tracheoesophageal fistula that were diagnosed in a single unit over a 6-year period. The variables assessed were age at presentation, presenting symptoms, time to diagnosis, investigations, and time to surgical repair of H-type fistula. The investigations leading to a definitive diagnosis are assessed and discussed. RESULTS: Between 1998 and 2004, five cases of H-type tracheoesophageal fistula presented to our unit. All cases had an upper gastrointestinal contrast study/tube esophagogram. In addition, four cases had a chest radiograph, three cases had a bronchoscopy, and one case an esophagoscopy. The median delay from the time of first presentation to diagnosis of H-type tracheoesophageal fistula was 14 days (7-58 days). Median age at surgery was 15 days (8-60 days). CONCLUSION: Although symptoms are usually present from birth, the diagnosis of H-type fistula is difficult and often delayed. The various diagnostic techniques are not entirely reliable and fistula identification can be elusive. The authors present recommendations for the diagnostic work-up, which may increase the diagnostic potential and avoid unnecessary delays in the diagnosis and management of H fistula.

The "Lasso-o" tape: stretchability and observer variability in head circumference measurement.

Head circumference is an important clinical measurement in children. The stretchability of the Lasso-o tape and the intra- and inter-observer reproducibility of measurements using it were investigated. Old Lasso-o tapes stretch significantly. The intra-class coefficients were 0.999 for intra-observer and 0.979 for inter-observer measurements. Nonetheless in 9% of measurements inter-observer variability was over 1 cm.

Heterotrophic plate count measurement in drinking water safety management: report of an Expert Meeting Geneva, 24-25 April 2002.

A group of microbiology and public health experts including regulatory and medical expertise was convened in Geneva, Switzerland, 25-26 April 2002 to consider the utility of heterotrophic plate count (HPC) measurements in addressing drinking water quality and safety. The group was convened following the NSF International/World Health Organization Symposium on HPC Bacteria in Drinking Water--Public Health Implications? The Expert Meeting was attended by 31 participants from Australia, Canada, France, Germany, Italy, Japan, the Netherlands, South Africa, Switzerland, UK and USA.

Providing clean water, keeping water clean: an integrated approach.

Millions of people, most of whom are children in developing countries, die of basic hygiene-related diseases every year. Interventions in hygiene, sanitation and water supply have been shown to control disease burden. Universal access to improved water sources and basic sanitation remains elusive but is an important long-term goal. Studies have shown that improving the microbiological quality of household water by on-site or point-of-use treatment and safe storage in improved vessels reduces diarrhoeal and other waterborne diseases in communities and households of developing and developed countries. The extent to which improving drinking water quality at the household level reduces diarrhoeal disease probably depends on a variety of technology-related and site-specific environmental and demographic factors that require further investigation, characterisation and analyses.

Not just a drop in the bucket: expanding access to point-of-use water treatment systems.

Since 1990, the number of people without access to safe water sources has remained constant at approximately 1.1 billion, of whom approximately 2.2 million die of waterborne disease each year. In developing countries, population growth and migrations strain existing water and sanitary infrastructure and complicate planning and construction of new infrastructure. Providing safe water for all is a long-term goal; however, relying only on time- and resource-intensive centralized solutions such as piped, treated water will leave hundreds of millions of people without safe water far into the future. Self-sustaining, decentralized approaches to making drinking water safe, including point-of-use chemical and solar disinfection, safe water storage, and behavioral change, have been widely field-tested. These options target the most affected, enhance health, contribute to development and productivity, and merit far greater priority for rapid implementation.

Waterborne health risks and the WHO perspective.

The benefits of improved water and sanitation include both health and non-health effects. The direct health benefits are related to two contrasting roles of water: that of disease vector when it carries pathogens; and that of health mediator through its use in personal and domestic hygiene. Indirect effects related to health include for example improved quality of life and decreased expenditure on medical expenses. Non-health effects include time savings for productive activity or education. The fact that the health impact of inadequate water supply services, especially in the developing world, has never been established is recognised (Troare, 1992) and recent work highlights unrecognised health burdens elsewhere--both from apparently good quality supplies (Payment et al., 1991; Payment et al., 1997); and from outbreaks of disease (Ford and Colwell, 1996). This paper looks at the WHO perspective on waterborne health risks and is divided into three main sections: our knowledge of the existing situation; recognised and emerging priorities arising from the changing context; and the availability of approaches and tools to meet the recognised and emerging priorities.