Water Supply Interruptions Are Associated with More Frequent Stressful Behaviors and Emotions but Mitigated by Predictability: A Multisite Study.

Water supply interruptions contribute to household water insecurity. Unpredictable interruptions may particularly exacerbate water insecurity, as uncertainty limits households' ability to optimize water collection and storage or to modify other coping behaviors. This study used regression models of survey data from 2873 households across 10 sites in 9 middle-income countries to assess whether water supply interruptions and the predictability of interruptions were related to composite indicators of stressful behaviors and emotional distress. More frequent water service interruptions were associated with more frequent emotional distress (ß = 0.49, SE = 0.05, P < 0.001) and stressful behaviors (ß = 0.39, SE = 0.06, P < 0.001). Among households that experienced interruptions, predictability mitigated these respective relationships by approximately 25 and 50%. Where the provision of continuous water supplies is challenged by climate change, population growth, and poor management, water service providers may be able to mitigate some psychosocial consequences of intermittency through scheduled intermittency and communication about water supply interruptions. Service providers unable to supply continuous water should optimize intermittent water delivery to reduce negative impacts on users, and global monitoring regimes should account for intermittency and predictability in post-2030 water service metrics to better reflect household water insecurity experiences.

Identification of p53-target genes in human papillomavirus-associated head and neck cancer by integrative bioinformatics analysis.

Introduction: Head and neck cancer (HNC) is a highly prevalent and heterogeneous malignancy. Although extensive efforts have been made to advance its treatment, the prognosis remained poor with increased mortality. Human papillomaviruses (HPV) have been associated with high risk in HNC. TP53, a tumor suppressor, is the most frequently altered gene in HNC, therefore, investigating its target genes for the identification of novel biomarkers or therapeutic targets in HPV-related HNC progression is highly recommended. Methods: Transcriptomic profiles from three independent gene expression omnibus (GEO) datasets, including 44 HPV+ and 70 HPV- HNC patients, were subjected to integrative statistical and Bioinformatics analyses. For the top-selected marker, further in-silico validation in TCGA and GTEx databases and experimental validation in 65 (51 HPV- and 14 HPV+) subjects with histologically confirmed head and neck squamous cell carcinoma (HNSCC) have been performed. Results: A total of 498 differentially expressed genes (DEGs) were identified including 291 up-regulated genes and 207 down-regulated genes in HPV+ compared to HPV- HNSCC patients. Functional annotations and gene set enrichment analysis (GSEA) showed that the up-regulated genes were significantly involved in p53-related pathways. The integrative analysis between the Hub-genes identified in the complex protein-protein network and the top frequent genes resulting from GSEA showed an intriguing correlation with five biomarkers which are EZH2, MDM2, PCNA, STAT5A and TYMS. Importantly, the MDM2 gene showed the highest gene expression difference between HPV+ and HPV- HNSCC (Average log2FC = 1.89). Further in-silico validation in a large HNSCC cohort from TCGA and GTEx databases confirmed the over-expression of MDM2 in HPV+ compared to HPV- HNSCC patients (p = 2.39E-05). IHC scoring showed that MDM2 protein expression was significantly higher in HPV+ compared to HPV- HNSCC patients (p = 0.031). Discussion: Our findings showed evidence that over-expression of MDM2, proto-oncogene, may affect the occurrence and proliferation of HPV-associated HNSCC by disturbing the p53-target genes and consequently the p53-related pathways.

COVID-19 outbreaks analysis in the Valencian Region of Spain in the prelude of the third wave.

Introduction: The COVID-19 pandemic has led to unprecedented social and mobility restrictions on a global scale. Since its start in the spring of 2020, numerous scientific papers have been published on the characteristics of the virus, and the healthcare, economic and social consequences of the pandemic. However, in-depth analyses of the evolution of single coronavirus outbreaks have been rarely reported. Methods: In this paper, we analyze the main properties of all the tracked COVID-19 outbreaks in the Valencian Region between September and December of 2020. Our analysis includes the evaluation of the origin, dynamic evolution, duration, and spatial distribution of the outbreaks. Results: We find that the duration of the outbreaks follows a power-law distribution: most outbreaks are controlled within 2 weeks of their onset, and only a few last more than 2 months. We do not identify any significant differences in the outbreak properties with respect to the geographical location across the entire region. Finally, we also determine the cluster size distribution of each infection origin through a Bayesian statistical model. Discussion: We hope that our work will assist in optimizing and planning the resource assignment for future pandemic tracking efforts.

Problem instances dataset of a real-world sequencing problem with transition constraints and asymmetric costs.

This data article describes 30 instances of the real-world problem of sequencing steel coils in a continuous galvanizing line. Each instance is represented by a cost matrix that gives information of the cost of sequencing each pair of coils or items together (e.g. a transition). Some transitions are forbidden due to technical limitations of the line and/or because of the properties of the coils, what makes the problem more challenging. These costs were previously obtained by a cost model that estimates the final cost of each transition for a set of coils to be sequenced in the line. Although the instances come from this real context, the problem can be theoretically seen as finding a minimum cost Hamiltonian path (e.g. a minimum cost feasible production sequence with all the coils appearing just once). It is a well-known NP-Hard combinatorial optimization problem. Since these instances represent real challenges found in the industry, they can be very useful for algorithm development and testing. Due to the cost distributions obtained for the given coils, just finding a feasible sequence can be a challenging task, especially for some types of approximate algorithms (Alvarez-Gil et al., 2022).

Health-related economic benefits of universal access to piped water in Arctic communities: Estimates for the Yukon-Kuskokwim Delta region of Alaska.

This paper presents estimates of the potential health-related economic benefits of providing universal access to in-home water and sanitation services to households in rural Alaska. In particular, we use data on disease incidence rates, health care costs, and local estimates of the impact of piped water on disease reduction to estimate the potential health-related economic benefits of providing universal access to piped water in the Yukon Kuskokwim (Y.K.) Delta region of Alaska. We include estimates of avoided treatment and diagnosis costs as well as private benefits associated with reduced morbidity and mortality associated with improved access to in-home piped water. To our knowledge, these are the first estimates of the economic benefits of improved access to water and sanitation in rural Alaska and the Arctic. Our analysis suggests increased access to in-home piped water in the region may yield substantial reductions in direct medical expenses incurred by public agencies and families, as well as reductions in time and travel costs associated with improved health outcomes. These benefits, along with the array of health and non-health-related benefits not included in our analysis, may provide new impetus to expanding access to high-quality water and sanitation services in the region.

Seasonal variations of electrical signals of Pinus halepensis Mill. in Mediterranean forests in dependence on climatic conditions.

The temporal evolution of the electrical signal generated by Pinus halepensis was measured in a sample of 15 trees. Weekly experiments were carried out during a long-term campaign lasting over a year, while trials with a high frequency of measurements were also performed during several days. In the latter case, day-night oscillations of the electrical magnitudes were observed. Additionally, punctual meteorological events such as rainfall and electrical storms affect the electrical signal as well.The measured electrical intensity grows exponentially with the voltage. In fact, no electrical intensity that exceeds the threshold of 0.01 µA is gathered when voltage values are lower than 0.6 V. In general, higher electrical signals were gathered during the rainy seasons with moderate temperatures; while very low signals, including few measures of zero intensity, were obtained during the most stressful periods over the year, mainly by mid-summer.There is a strong correlation between the rainfall and the electrical signal. The rain-intensity correlation, together with sustained intensity values during the reproductive period in spring, suggests that this electrical magnitude could be an indicator of the physiological state of the tree and thus used for in situ and minimally invasive forest monitoring.

Access to water, sanitation and hygiene services in health facilities in sub-Saharan Africa 2013-2018: Results of health facility surveys and implications for COVID-19 transmission.

BACKGROUND: The COVID-19 pandemic has highlighted important needs in water, sanitation and hygiene (WASH) services and standard practices for infection prevention and control in sub-Saharan Africa. We assessed the availability of WASH and standard precautions for infection prevention in health facilities across 18 countries in sub-Saharan Africa, as well as inequalities by location (rural/urban) and managing authority (public/private). Data from health facility surveys conducted between 2013 and 2018 in 18 sub-Saharan African countries were used to estimate the access to an improved water source within 500 m, an improved toilet, soap and running water or alcohol-based hand rub, and standard precautions for infection prevention at health facilities. Rural-urban differences and public-private differences in access to services were calculated. We also compared population level access to health facility access to services. RESULT: Overall, 16,456 health facilities from 18 countries were included. Across countries, an estimated 88 % had an improved water source, 94 % had an improved toilet, 74 % had soap and running water or alcohol-based hand rub, and 17 % had standard precautions for infection prevention available. There was wide variability in access to water, sanitation and hygiene services between rural and urban health facilities and between public and private facilities, with consistently lower access in both rural and public facilities. In both rural and urban areas, access to water, sanitation and hygiene services was ubiquitously better at health facilities than households. CONCLUSIONS: Availability of WASH services in health facilities in sub-Saharan Africa has improved but remains below the global target of 80 % in many countries. Ensuring adequate access to WASH services and enforcing adherence to safety and hygiene practices in health facilities will be essential to minimize the risk of COVID-19 transmission.

Development and application of tools to cost the delivery of environmental health services in healthcare facilities: a financial analysis in urban Malawi.

BACKGROUND: Environmental health services (EHS) in healthcare facilities (HCFs) are critical for providing a safe, functional healthcare environment, but little is known about their costs. Poor understanding of costs impedes progress towards universal access of EHS in HCFs. We developed frameworks of essential expenses required to provide EHS and conducted an ex-post financial analysis of EHS in a network of medical research and training facilities in Lilongwe, Malawi, serving an estimated 42,000 patients annually through seven outpatient buildings. METHODS: We estimated the cost of providing the following EHS: water, sanitation, hygiene, personal protective equipment use at the point of care, waste management, cleaning, laundry, and vector control. We developed frameworks of essential outputs and inputs for each EHS through review of international guidelines and standards, which we used to identify expenses required for EHS delivery and evaluate the completeness of costs data in our case study. For costing, we use a mixed-methods approach, applying qualitative interviews to understand facility context and review of electronic records to determine costs. We calculated initial costs to establish EHS and annual operations and maintenance. RESULTS: Available records contained little information on the upfront, capital costs associated with establishing EHS. Annual operations and maintenance totaled USD 220,427 for all EHS across all facilities (USD 5.21 per patient encounter), although costs of many essential inputs were missing from records. Annual operations and maintenance costs were highest for cleaning (USD 69,372) and waste management (USD 46,752). DISCUSSION: Missing expenses suggests that documented costs are substantial underestimates. Costs to establish services were missing predominantly because purchases pre-dated electronic records. Annual operations and maintenance costs were incomplete primarily because administrative records did not record sufficient detail to disaggregate and attribute expenses. CONCLUSIONS: Electronic health information systems have potential to support efficient data collection. However, we found that existing records systems were decentralized and poorly suited to identify EHS costs. Our research suggests a need to better code and disaggregate EHS expenses to properly leverage records for costing. Frameworks developed in this study are a potential tool to develop more accurate estimates of the cost of providing EHS in HCFs.

Heterologous Production of Glycine Betaine Using Synechocystis sp. PCC 6803-Based Chassis Lacking Native Compatible Solutes.

Among compatible solutes, glycine betaine has various applications in the fields of nutrition, pharmaceuticals, and cosmetics. Currently, this compound can be extracted from sugar beet plants or obtained by chemical synthesis, resulting in low yields or high carbon footprint, respectively. Hence, in this work we aimed at exploring the production of glycine betaine using the unicellular cyanobacterium Synechocystis sp. PCC 6803 as a photoautotrophic chassis. Synechocystis mutants lacking the native compatible solutes sucrose or/and glucosylglycerol-∆sps, ∆ggpS, and ∆sps∆ggpS-were generated and characterized. Under salt stress conditions, the growth was impaired and accumulation of glycogen decreased by ∼50% whereas the production of compatible solutes and extracellular polymeric substances (capsular and released ones) increased with salinity. These mutants were used as chassis for the implementation of a synthetic device based on the metabolic pathway described for the halophilic cyanobacterium Aphanothece halophytica for the production of the compatible solute glycine betaine. Transcription of ORFs comprising the device was shown to be stable and insulated from Synechocystis' native regulatory network. Production of glycine betaine was achieved in all chassis tested, and was shown to increase with salinity. The introduction of the glycine betaine synthetic device into the ∆ggpS background improved its growth and enabled survival under 5% NaCl, which was not observed in the absence of the device. The maximum glycine betaine production [64.29 µmol/gDW (1.89 µmol/mg protein)] was reached in the ∆ggpS chassis grown under 3% NaCl. Taking into consideration this production under seawater-like salinity, and the identification of main key players involved in the carbon fluxes, this work paves the way for a feasible production of this, or other compatible solutes, using optimized Synechocystis chassis in a pilot-scale.

Reconstruction of the absorption spectrum of Synechocystis sp. PCC 6803 optical mutants from the in vivo signature of individual pigments.

In this work, we reconstructed the absorption spectrum of different Synechocystis sp. PCC 6803 optical strains by summing the computed signature of all pigments present in this organism. To do so, modifications to in vitro pigment spectra were first required: namely wavelength shift, curve smoothing, and the package effect calculation derived from high pigment densities were applied. As a result, we outlined a plausible shape for the in vivo absorption spectrum of each chromophore. These are flatter and slightly broader in physiological conditions yet the mean weight-specific absorption coefficient remains identical to the in vitro conditions. Moreover, we give an estimate of all pigment concentrations without applying spectrophotometric correlations, which are often prone to error. The computed cell spectrum reproduces in an accurate manner the experimental spectrum for all the studied wavelengths in the wild-type, Olive, and PAL strain. The gathered pigment concentrations are in agreement with reported values in literature. Moreover, different illumination set-ups were evaluated to calculate the mean absorption cross-section of each chromophore. Finally, a qualitative estimate of light-limited cellular growth at each wavelength is given. This investigation describes a novel way to approach the cell absorption spectrum and shows all its inherent potential for photosynthesis research.

Cost effectiveness of community led total sanitation in Ethiopia and Ghana.

We conducted cost effectiveness analyses of four different CLTS interventions implemented in Ethiopia and Ghana. In each country, a pilot approach in which additional local actors were trained in CLTS facilitation was compared to the conventional approach. Data were collected using bottom-up costing, household surveys, and observations. We assessed variability of cost effectiveness from a societal perspective for latrine ownership and latrine use outcomes in different contexts. Cost effectiveness ranged from $34-$1897 per household ($5.85-$563 per person) gaining access to a private latrine or stopping open defecation, depending on the intervention, context, and outcome considered. For three out of four interventions, CLTS appeared more cost effective at reducing open defecation than at increasing latrine ownership, although sensitivity analysis revealed considerable variation. The pilot approaches were more cost effective at reducing open defecation than conventional approaches in Ethiopia, but not in Ghana. CLTS has been promoted as a low-cost means of improving the ownership and use of sanitation facilities. In our study, the cost of CLTS per household gaining latrine access was slightly higher than in other studies, and the cost of CLTS per household stopping OD was slightly lower than in other studies. Our results show that aggregate measures mask considerable variability in costs and outcomes, and thus the importance of considering and reporting context and uncertainty in economic analysis of sanitation interventions.

The effects of quantity discounts on supply chain performance: Looking through the Bullwhip lens.

Quantity discounts are a common pricing mechanism to stimulate large orders. We explore their impact on the dynamic behaviour of production and distribution systems by studying key operational and economic metrics. In a three-echelon supply chain, we observe that the discount generally increases the Bullwhip Effect, which especially harms the manufacturer. The discount also reduces the retailer's purchase costs, but increases its inventory- and capacity-related costs. A key trade-off thus emerges, which manifests itself through a U-shaped relationship between the total cost and the discount acceptance parameter. In the light of this trade-off, we discuss how key factors should affect the retailer's willingness to pursue the discount. We observe that managers that need to deal with tougher environmental conditions, such as high demand uncertainty and long lead times, should be less reluctant to increase orders up to the discount quantity. We also discuss in detail other valuable insights for professionals, both from the perspective of sellers and buyers.

Forecasts of mortality and economic losses from poor water and sanitation in sub-Saharan Africa.

This paper presents country-level estimates of water, sanitation and hygiene (WASH)-related mortality and the economic losses associated with poor access to water and sanitation infrastructure in sub-Saharan Africa (SSA) from 1990 to 2050. We examine the extent to which the changes that accompany economic growth will "solve" water and sanitation problems in SSA and, if so, how long it will take. Our simulations suggest that WASH-related mortality will continue to differ markedly across countries in sub-Saharan Africa. In many countries, expected economic growth alone will not be sufficient to eliminate WASH-related mortality or eliminate the economic losses associated with poor access to water and sanitation infrastructure by 2050. In other countries, WASH-related mortality will sharply decline, although the economic losses associated with the time spent collecting water are forecast to persist. Overall, our findings suggest that in a subset of countries in sub-Saharan Africa (e.g., Angola, Niger, Sierra Leone, Chad and several others), WASH-related investments will remain a priority for decades and require a long-term, sustained effort from both the international community and national governments.

Community water service and incidence of respiratory, skin, and gastrointestinal infections in rural Alaska, 2013-2015.

BACKGROUND: Communities in rural Alaska have access to multiple types of water service (piped, vehicle-hauled, and self-hauled) and experience varying levels of water service coverage. We assessed the incidence rate of inpatient and outpatient infectious disease visits among communities with different water service types and coverage levels. METHODS: We classified ICD-9 codes for inpatient and outpatient visits to the Yukon-Kuskokwim Health Corporation facilities between 2013 and 2015 into six infectious disease categories. Using Poisson models, we compared the incidence of visits in each category across communities with differing water service coverage levels as defined by water service billing data for the same years. Using census data, we adjusted for community median household income, median age, crowding, and health aide staffing. RESULTS: We included 48 communities in this analysis. After adjusting for possible confounders, each 10% increase in piped water coverage was associated with a 4% lower incidence of pneumonia/influenza visits (adjusted incidence rate ratio [IRR] 0.96, 95% CI 0.93-0.98), a 2% lower incidence of other respiratory infection visits (adjusted IRR 0.98, 95% CI 0.97-0.99), an 8% lower incidence of methicillin-resistant Staphylococcus visits (adjusted IRR 0.92, 95% CI 0.87-0.97), and a 4% lower incidence of other skin infections visits (adjusted IRR 0.96, 95% CI 0.95-0.98). Each 10% increase in vehicle-hauled water coverage was associated with a 2% lower incidence of respiratory infection visits (adjusted IRR 0.98, 95% CI 0.97-0.996) and a 3% lower incidence of skin infection visits (adjusted IRR 0.97, 95% CI 0.95-0.99), also after adjustment. CONCLUSIONS: Higher levels of water service coverage were associated with lower incidence rates of visits for several infectious disease categories. These associations were more pronounced for communities with piped water service compared to vehicle-hauled water service.

On strategic choices faced by large pharmaceutical laboratories and their effect on innovation risk under fuzzy conditions.

OBJECTIVES: We develop a fuzzy evaluation model that provides managers at different responsibility levels in pharmaceutical laboratories with a rich picture of their innovation risk as well as that of competitors. This would help them take better strategic decisions around the management of their present and future portfolio of clinical trials in an uncertain environment. Through three structured fuzzy inference systems (FISs), the model evaluates the overall innovation risk of the laboratories by capturing the financial and pipeline sides of the risk. METHODS AND MATERIALS: Three FISs, based on the Mamdani model, determine the level of innovation risk of large pharmaceutical laboratories according to their strategic choices. Two subsystems measure different aspects of innovation risk while the third one builds on the results of the previous two. In all of them, both the partitions of the variables and the rules of the knowledge base are agreed through an innovative 2-tuple-based method. With the aid of experts, we have embedded knowledge into the FIS and later validated the model. RESULTS: In an empirical application of the proposed methodology, we evaluate a sample of 31 large pharmaceutical laboratories in the period 2008-2013. Depending on the relative weight of the two subsystems in the first layer (capturing the financial and the pipeline sides of innovation risk), we estimate the overall risk. Comparisons across laboratories are made and graphical surfaces are analyzed in order to interpret our results. We have also run regressions to better understand the implications of our results. CONCLUSIONS: The main contribution of this work is the development of an innovative fuzzy evaluation model that is useful for analyzing the innovation risk characteristics of large pharmaceutical laboratories given their strategic choices. The methodology is valid for carrying out a systematic analysis of the potential for developing new drugs over time and in a stable manner while managing the risks involved. We provide all the necessary tools and datasets to facilitate the replication of our system, which also may be easily applied to other settings.

[Feedback on the implementation of a departmental physical activity project for the elderly]. / Retour d'expérience sur la mise en œuvre d'une action départementale d'activité physique pour les seniors.

INTRODUCTION: Regular physical activity is nowadays recognized as one of the keys for ageing well. A number of interventions are therefore developed for this target group. The goal of this study was to examine the establishment and impact of a structured physical activity program for subjects aged 60 or more on a departmental scale and according to the point of view of different actors engaged. METHODS: The PAS Project (Prévention Active Senior), coordinated by a resource and expertise center, consisted of conceiving and implementing a structured physical activity program for subjects aged 60 or more. In every municipality, the program was conducted by a local sports instructor in partnership with a municipal representative. It consisted of 3 weekly sessions of physical activity (2 supervised and 1 individual) over a period of 3 months. The data was collected thanks to the tools developed for the evaluation. RESULTS: The program was conducted in 27 municipalities. A total of 586 participants enrolled in the program and 439 completed the final evaluation. This project allowed for the improvement of three main physical capacities (endurance, muscular strength, and balance) for most of the participants. At the end of the program, more than 50% of municipalities created or supported a long term physical activity offer for elderly. DISCUSSION: This study highlights the need of adapting this kind of intervention to the local context. It confirmed the interest of a combined individual and more general approach, as well as a cross-sectorial work in order to create the conditions for sustainable daily physical activity for the target group.

Perceptions of climate-related risk among water sector professionals in Africa-Insights from the 2016 African Water Association Congress.

The ability of water and wastewater utilities to provide safe and reliable water and sanitation services now and in the future will be determined, in part, by their resilience to climate change. Investment in infrastructure, planning, and operational practices that increase resilience are affected, in turn, by how water sector professionals perceive the risks posed to utilities by climate change and its related impacts. We surveyed water sector professionals at the 2016 African Water Association's Congress in Nairobi, Kenya to assess their perceptions of climate-specific and general risks that may disrupt utility service. We find that water sector professionals are most concerned about climate-specific and general risks that affect utility water supplies (quantity), followed by adequacy of utility infrastructure. We also find that professionals tend to rank climate-specific risks as less concerning than general risks facing utilities. Furthermore, non-utility professionals are more concerned about climate-specific risks and climate change in general than utility professionals. These findings highlight the multiple, competing risks utilities face and the need for adaptation strategies that simultaneously address climate-specific and general concerns of utilities.

Measuring the efficiency of large pharmaceutical companies: an industry analysis.

This paper evaluates the relative efficiency of a sample of 37 large pharmaceutical laboratories in the period 2008-2013 using a data envelopment analysis (DEA) approach. We describe in detail the procedure followed to select and construct relevant inputs and outputs that characterize the production and innovation activity of these pharmaceutical firms. Models are estimated with financial information from Datastream, including R&D investment, and the number of new drugs authorized by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) considering the time effect. The relative performances of these firms-taking into consideration the strategic importance of R&D-suggest that the pharmaceutical industry is a highly competitive sector given that there are many laboratories at the efficient frontier and many inefficient laboratories close to this border. Additionally, we use data from S&P Capital IQ to analyze 2071 financial transactions announced by our sample of laboratories as an alternative way to gain access to new drugs, and we link these transactions with R&D investment and DEA efficiency. We find that efficient laboratories make on average more financial transactions, and the relative size of each transaction is larger. However, pharmaceutical companies that simultaneously are more efficient and invest more internally in R&D announce smaller transactions relative to total assets.

Generation and Evaluation of a Genome-Scale Metabolic Network Model of Synechococcus elongatus PCC7942.

The reconstruction of genome-scale metabolic models and their applications represent a great advantage of systems biology. Through their use as metabolic flux simulation models, production of industrially-interesting metabolites can be predicted. Due to the growing number of studies of metabolic models driven by the increasing genomic sequencing projects, it is important to conceptualize steps of reconstruction and analysis. We have focused our work in the cyanobacterium Synechococcus elongatus PCC7942, for which several analyses and insights are unveiled. A comprehensive approach has been used, which can be of interest to lead the process of manual curation and genome-scale metabolic analysis. The final model, iSyf715 includes 851 reactions and 838 metabolites. A biomass equation, which encompasses elementary building blocks to allow cell growth, is also included. The applicability of the model is finally demonstrated by simulating autotrophic growth conditions of Synechococcus elongatus PCC7942.