Real-time multiobjective optimization of operation of water supply systems

The need for more efficient use of energy in water distribution systems is increasing constantly due to increasing energy prices. A new methodology for optimized real-time operation of a water distribution system is developed and presented here. The methodology is based on the integration of three models: (1) real-time demand forecasting model, (2) hydraulic simulation model of the system, and (3) optimization model. The optimization process is driven by the cost minimization of the energy used for pumping and the maximization of operational reliability. The latter is quantified using alternative measures into the optimization process in order to mimic the conservative attitude to pump scheduling often adopted by control room operators in real-life systems. Optimal pump schedules were generated by using a multialgorithmgenetically- adaptive-method (AMALGAM), hydraulic simulations are performed by using the EPANET2 model, and demand forecasting was performed by using the recently developed DAN2-H model. A number of other methodological developments are used to enable pump scheduling in real time. The new methodology is tested, verified, and demonstrated on the water distribution system of Araraquara, in the state of São Paulo, Brazil. The results obtained demonstrate that it is possible to achieve substantial energy cost savings (up to 13% relative to historical system operation) while simultaneously maintaining the level of supply reliability obtained by manually operating the water system.São Paulo Research Foundation (FAPESP)Coordination for the Improvement of Higher Education (CAPES)Brazilian Scientific and Technological Development Council (CNPq)Araraquara’s Autonomous Department of Water and Sewage (DAAE-Araraquara, SP, Brazil

PCR colorimetric dot-blot assay and clinical pretest probability for diagnosis of Pulmonary Tuberculosis in Smear-Negative patients

<p>Abstract</p> <p>Background</p> <p>Smear-negative pulmonary tuberculosis (SNPTB) accounts for 30% of Pulmonary Tuberculosis (PTB) cases reported annually in developing nations. Polymerase chain reaction (PCR) may provide an alternative for the rapid detection of <it>Mycobacterium tuberculosis </it>(MTB); however little data are available regarding the clinical utility of PCR in SNPTB, in a setting with a high burden of TB/HIV co-infection.</p> <p>Methods</p> <p>To evaluate the performance of the PCR dot-blot in parallel with pretest probability (Clinical Suspicion) in patients suspected of having SNPTB, a prospective study of 213 individuals with clinical and radiological suspicion of SNPTB was carried out from May 2003 to May 2004, in a TB/HIV reference hospital. Respiratory specialists estimated the pretest probability of active disease into high, intermediate, low categories. Expectorated sputum was examined by direct microscopy (Ziehl-Neelsen staining), culture (Lowenstein Jensen) and PCR dot-blot. Gold standard was based on culture positivity combined with the clinical definition of PTB.</p> <p>Results</p> <p>In smear-negative and HIV subjects, active PTB was diagnosed in 28.4% (43/151) and 42.2% (19/45), respectively. In the high, intermediate and low pretest probability categories active PTB was diagnosed in 67.4% (31/46), 24% (6/25), 7.5% (6/80), respectively. PCR had sensitivity of 65% (CI 95%: 50%–78%) and specificity of 83% (CI 95%: 75%–89%). There was no difference in the sensitivity of PCR in relation to HIV status. PCR sensitivity and specificity among non-previously TB treated and those treated in the past were, respectively: 69%, 43%, 85% and 80%. The high pretest probability, when used as a diagnostic test, had sensitivity of 72% (CI 95%:57%–84%) and specificity of 86% (CI 95%:78%–92%). Using the PCR dot-blot in parallel with high pretest probability as a diagnostic test, sensitivity, specificity, positive and negative predictive values were: 90%, 71%, 75%, and 88%, respectively. Among non-previously TB treated and HIV subjects, this approach had sensitivity, specificity, positive and negative predictive values of 91%, 79%, 81%, 90%, and 90%, 65%, 72%, 88%, respectively.</p> <p>Conclusion</p> <p>PCR dot-blot associated with a high clinical suspicion may provide an important contribution to the diagnosis of SNPTB mainly in patients that have not been previously treated attended at a TB/HIV reference hospital.</p

Multicenter study of the natural history and therapeutic responses of patients with chikungunya, focusing on acute and chronic musculoskeletal manifestations - a study protocol from the clinical and applied research in Chikungunya (REPLICK network)

BACKGROUND: Chikungunya is associated with high morbidity and the natural history of symptomatic infection has been divided into three phases (acute, post-acute, and chronic) according to the duration of musculoskeletal symptoms. Although this classification has been designed to help guide therapeutic decisions, it does not encompass the complexity of the clinical expression of the disease and does not assist in the evaluation of the prognosis of severity nor chronic disease. Thus, the current challenge is to identify and diagnose musculoskeletal disorders and to provide the optimal treatment in order to prevent perpetuation or progression to a potentially destructive disease course. METHODS: The study is the first product of the Clinical and Applied Research Network in Chikungunya (REPLICK). This is a prospective, outpatient department-based, multicenter cohort study in Brazil. Four work packages were defined: i. Clinical research; ii) Translational Science - comprising immunology and virology streams; iii) Epidemiology and Economics; iv) Therapeutic Response and clinical trials design. Scheduled appointments on days 21 (D21) ± 7 after enrollment, D90 ± 15, D120 ± 30, D180 ± 30; D360 ± 30; D720 ± 60, and D1080 ± 60 days. On these visits a panel of blood tests are collected in addition to the clinical report forms to obtain data on socio-demographic, medical history, physical examination and questionnaires devoted to the evaluation of musculoskeletal manifestations and overall health are performed. Participants are asked to consent for their specimens to be maintained in a biobank. Aliquots of blood, serum, saliva, PAXgene, and when clinically indicated to be examined, synovial fluid, are stored at -80° C. The study protocol was submitted and approved to the National IRB and local IRB at each study site. DISCUSSION: Standardized and harmonized patient cohorts are needed to provide better estimates of chronic arthralgia development, the clinical spectra of acute and chronic disease and investigation of associated risk factors. This study is the largest evaluation of the long-term sequelae of individuals infected with CHIKV in the Brazilian population focusing on musculoskeletal manifestations, mental health, quality of life, and chronic pain. This information will both define disease burden and costs associated with CHIKV infection, and better inform therapeutic guidelines

SDG Final Decade of Action: Resilient Pathways to Build Back Better from High-Impact Low-Probability (HILP) Events

Data Availability Statement: Not applicable.Copyright © 2022 by the authors. The 2030 Sustainable Development Goals (SDGs) offer a blueprint for global peace and prosperity, while conserving natural ecosystems and resources for the planet. However, factors such as climate-induced weather extremes and other High-Impact Low-Probability (HILP) events on their own can devastate lives and livelihoods. When a pandemic affects us, as COVID-19 has, any concurrent hazards interacting with it highlight additional challenges to disaster and emergency management worldwide. Such amplified effects contribute to greater societal and environmental risks, with cross-cutting impacts and exposing inequities. Hence, understanding how a pandemic affects the management of concurrent hazards and HILP is vital in disaster risk reduction practice. This study reviews the contemporary literature and utilizes data from the Emergency Events Database (EM-DAT) to unpack how multiple extreme events have interacted with the coronavirus pandemic and affected the progress in achieving the SDGs. This study is especially urgent, given the multidimensional societal impacts of the COVID-19 pandemic amidst climate change. Results indicate that mainstreaming risk management into development planning can mitigate the adverse effects of disasters. Successes in addressing compound risks have helped us understand the value of new technologies, such as the use of drones and robots to limit human exposure. Enhancing data collection efforts to enable inclusive sentinel systems can improve surveillance and effective response to future risk challenges. Stay-at-home policies put in place during the pandemic for virus containment have highlighted the need to holistically consider the built environment and socio-economic exigencies when addressing the pandemic’s physical and mental health impacts, and could also aid in the context of increasing climate-induced extreme events. As we have seen, such policies, services, and technologies, along with good nutrition, can significantly help safeguard health and well-being in pandemic times, especially when simultaneously faced with ubiquitous climate-induced extreme events. In the final decade of SDG actions, these measures may help in efforts to “Leave No One Behind”, enhance human–environment relations, and propel society to embrace sustainable policies and lifestyles that facilitate building back better in a post-pandemic world. Concerted actions that directly target the compounding effects of different interacting hazards should be a critical priority of the Sendai Framework by 2030.This research received no external funding

AAV Exploits Subcellular Stress Associated with Inflammation, Endoplasmic Reticulum Expansion, and Misfolded Proteins in Models of Cystic Fibrosis

Barriers to infection act at multiple levels to prevent viruses, bacteria, and parasites from commandeering host cells for their own purposes. An intriguing hypothesis is that if a cell experiences stress, such as that elicited by inflammation, endoplasmic reticulum (ER) expansion, or misfolded proteins, then subcellular barriers will be less effective at preventing viral infection. Here we have used models of cystic fibrosis (CF) to test whether subcellular stress increases susceptibility to adeno-associated virus (AAV) infection. In human airway epithelium cultured at an air/liquid interface, physiological conditions of subcellular stress and ER expansion were mimicked using supernatant from mucopurulent material derived from CF lungs. Using this inflammatory stimulus to recapitulate stress found in diseased airways, we demonstrated that AAV infection was significantly enhanced. Since over 90% of CF cases are associated with a misfolded variant of Cystic Fibrosis Transmembrane Conductance Regulator (ΔF508-CFTR), we then explored whether the presence of misfolded proteins could independently increase susceptibility to AAV infection. In these models, AAV was an order of magnitude more efficient at transducing cells expressing ΔF508-CFTR than in cells expressing wild-type CFTR. Rescue of misfolded ΔF508-CFTR under low temperature conditions restored viral transduction efficiency to that demonstrated in controls, suggesting effects related to protein misfolding were responsible for increasing susceptibility to infection. By testing other CFTR mutants, G551D, D572N, and 1410X, we have shown this phenomenon is common to other misfolded proteins and not related to loss of CFTR activity. The presence of misfolded proteins did not affect cell surface attachment of virus or influence expression levels from promoter transgene cassettes in plasmid transfection studies, indicating exploitation occurs at the level of virion trafficking or processing. Thus, we surmised that factors enlisted to process misfolded proteins such as ΔF508-CFTR in the secretory pathway also act to restrict viral infection. In line with this hypothesis, we found that AAV trafficked to the microtubule organizing center and localized near Golgi/ER transport proteins. Moreover, AAV infection efficiency could be modulated with siRNA-mediated knockdown of proteins involved in processing ΔF508-CFTR or sorting retrograde cargo from the Golgi and ER (calnexin, KDEL-R, β-COP, and PSMB3). In summary, our data support a model where AAV exploits a compromised secretory system and, importantly, underscore the gravity with which a stressed subcellular environment, under internal or external insults, can impact infection efficiency

Reproductive health and access to healthcare facilities: risk factors for depression and anxiety in women with an earthquake experience

<p>Abstract</p> <p>Background</p> <p>The reproductive and mental health of women contributes significantly to their overall well-being. Three of the eight Millennium Development Goals are directly related to reproductive and sexual health while mental disorders make up three of the ten leading causes of disease burden in low and middle-income countries. Among mental disorders, depression and anxiety are two of the most prevalent. In the context of slower progress in achieving Millennium Development Goals in developing countries and the ever-increasing man-made and natural disasters in these areas, it is important to understand the association between reproductive health and mental health among women with post-disaster experiences.</p> <p>Methods</p> <p>This was a cross-sectional study with a sample of 387 women of reproductive age (15-49 years) randomly selected from the October 2005 earthquake affected areas of Pakistan. Data on reproductive health was collected using the Centers for Disease Control reproductive health assessment toolkit. Depression and anxiety were measured using the Hopkins Symptom Checklist-25, while earthquake experiences were captured using the Harvard Trauma Questionnaire. The association of either depression or anxiety with socio-demographic variables, earthquake experiences, reproductive health and access to health facilities was estimated using multivariate logistic regression.</p> <p>Results</p> <p>Post-earthquake reproductive health events together with economic deprivation, lower family support and poorer access to health care facilities explained a significant proportion of differences in the experiencing of clinical levels of depression and anxiety. For instance, women losing resources for subsistence, separation from family and experiencing reproductive health events such as having a stillbirth, having had an abortion, having had abnormal vaginal discharge or having had genital ulcers, were at significant risk of depression and anxiety.</p> <p>Conclusion</p> <p>The relationship between women's post-earthquake mental health and reproductive health, socio-economic status, and health care access is complex and explained largely by the socio-cultural role of women. It is suggested that interventions that consider gender differences and that are culturally appropriate are likely to reduce the incidence.</p

Commercial Nucleic-Acid Amplification Tests for Diagnosis of Pulmonary Tuberculosis in Respiratory Specimens: Meta-Analysis and Meta-Regression

BACKGROUND: Hundreds of studies have evaluated the diagnostic accuracy of nucleic-acid amplification tests (NAATs) for tuberculosis (TB). Commercial tests have been shown to give more consistent results than in-house assays. Previous meta-analyses have found high specificity but low and highly variable estimates of sensitivity. However, reasons for variability in study results have not been adequately explored. We performed a meta-analysis on the accuracy of commercial NAATs to diagnose pulmonary TB and meta-regression to identify factors that are associated with higher accuracy. METHODOLOGY/PRINCIPAL FINDINGS: We identified 2948 citations from searching the literature. We found 402 articles that met our eligibility criteria. In the final analysis, 125 separate studies from 105 articles that reported NAAT results from respiratory specimens were included. The pooled sensitivity was 0.85 (range 0.36-1.00) and the pooled specificity was 0.97 (range 0.54-1.00). However, both measures were significantly heterogeneous (p<.001). We performed subgroup and meta-regression analyses to identify sources of heterogeneity. Even after stratifying by type of commercial test, we could not account for the variability. In the meta-regression, the threshold effect was significant (p = .01) and the use of other respiratory specimens besides sputum was associated with higher accuracy. CONCLUSIONS/SIGNIFICANCE: The sensitivity and specificity estimates for commercial NAATs in respiratory specimens were highly variable, with sensitivity lower and more inconsistent than specificity. Thus, summary measures of diagnostic accuracy are not clinically meaningful. The use of different cut-off values and the use of specimens other than sputum could explain some of the observed heterogeneity. Based on these observations, commercial NAATs alone cannot be recommended to replace conventional tests for diagnosing pulmonary TB. Improvements in diagnostic accuracy, particularly sensitivity, need to be made in order for this expensive technology to be worthwhile and beneficial in low-resource countries

Velocity-space sensitivity of the time-of-flight neutron spectrometer at JET

The velocity-space sensitivities of fast-ion diagnostics are often described by so-called weight functions. Recently, we formulated weight functions showing the velocity-space sensitivity of the often dominant beam-target part of neutron energy spectra. These weight functions for neutron emission spectrometry (NES) are independent of the particular NES diagnostic. Here we apply these NES weight functions to the time-of-flight spectrometer TOFOR at JET. By taking the instrumental response function of TOFOR into account, we calculate time-of-flight NES weight functions that enable us to directly determine the velocity-space sensitivity of a given part of a measured time-of-flight spectrum from TOFOR