Acoustic Energy Harvesting and Sensing via Electrospun PVDF Nanofiber Membrane

This paper introduces a new usage of piezoelectric poly (vinylidene fluoride) (PVDF) electrospun nanofiber (NF) membrane as a sensing unit for acoustic signals. In this work, an NF mat has been used as a transducer to convert acoustic signals into electric voltage outcomes. The detected voltage has been analyzed as a function of both frequency and amplitude of the excitation acoustic signal. Additionally, the detected AC signal can be retraced as a function of both frequency and amplitude with some wave distortion at relatively higher amplitudes and within a certain acoustic spectrum region. Meanwhile, the NFs have been characterized through piezoelectric responses, beta sheet calculations and surface morphology. This work is promising as a low-cost and innovative solution to harvest acoustic signals coming from wide resources of sound and noise

(Review Article*) Construction and Validation of Problem-Solving Ability Test

The study focused on the construction and validation of a problem-solving ability test. The test consists of 36 multiple choice items regarding numerical and reasoning ability tested on 810 students. The preliminary instrument consists of 46 multiple choice items was tested on 352 secondary school students. After the refinement of items using different procedures, 36 items were selected. The construction and development of the test was done by expert review, preliminary draft, item analysis, selection of items, preparation of final test, norms, validity, and reliability of the test. The Cranach’s (α) and split-half reliability of the test as found 0.909and 0.890 respectively with the intrinsic and criterion validity of the test was found to be 0.953and 0.781

(Review Article*) Construction and Validation of Problem-Solving Ability Test

The study focused on the construction and validation of a problem-solving ability test. The test consists of 36 multiple choice items regarding numerical and reasoning ability tested on 810 students. The preliminary instrument consists of 46 multiple choice items was tested on 352 secondary school students. After the refinement of items using different procedures, 36 items were selected. The construction and development of the test was done by expert review, preliminary draft, item analysis, selection of items, preparation of final test, norms, validity, and reliability of the test. The Cranach’s (α) and split-half reliability of the test as found 0.909and 0.890 respectively with the intrinsic and criterion validity of the test was found to be 0.953and 0.781

P66shc and its downstream Eps8 and Rac1 proteins are upregulated in esophageal cancers

Members of Shc (src homology and collagen homology) family, p46shc, p52shc, p66shc have known to be related to cell proliferation and carcinogenesis. Whereas p46shc and p52shc drive the reaction forward, the role of p66shc in cancers remains to be understood clearly. Hence, their expression in cancers needs to be evaluated carefully so that Shc analysis may provide prognostic information in the development of carcinogenesis. In the present study, the expression of p66shc and its associate targets namely Eps8 (epidermal pathway substrate 8), Rac1 (ras-related C3 botulinum toxin substrate1) and Grb2 (growth factor receptor bound protein 2) were examined in fresh tissue specimens from patients with esophageal squamous cell carcinoma and esophageal adenocarcinoma using western blot analysis. A thorough analysis of both esophageal squamous cell carcinoma and adenocarcinoma showed p66shc expression to be significantly higher in both types of carcinomas as compared to the controls. The controls of adenocarcinoma show a higher basal expression level of p66shc as compared to the controls of squamous cell carcinoma. The expression level of downstream targets of p66shc i.e., eps8 and rac1 was also found to be consistently higher in human esophageal carcinomas, and hence correlated positively with p66shc expression. However the expression of grb2 was found to be equal in both esophageal squamous cell carcinoma and adenocarcinoma. The above results suggest that the pathway operated by p66shc in cancers does not involve the participation of Ras and Grb2 as downstream targets instead it operates the pathway involving Eps8 and Rac1 proteins. From the results it is also suggestive that p66shc may have a role in the regulation of esophageal carcinomas and represents a possible mechanism of signaling for the development of squamous cell carcinoma and adenocarcinoma of esophagus

EHD1 is Required for IGF-1R-mediated Oncogenic Signaling in Ewing Sarcoma

Background and Significance: Ewing Sarcoma (EWS) is the second most common malignant bone tumor of children and adolescents. Patients with metastatic or recurrent disease have very poor outcomes. The receptor tyrosine kinase(RTK) insulin-like-growth-factor-1-receptor (IGF-1R) is upregulated in 93% of EWS patients with anti-IGF-1R antibodies and kinase inhibitors in clinical studies. However, with only ~10% of patients achieving objective responses, delineation of novel pathways that facilitate IGF-1R-driven oncogenesis in EWS could provide avenues for more effective therapy. The RTK levels and compartmentalization at the cell surface determine their access to growth factors, thus dictating the downstream oncogenic signaling. Our lab has demonstrated that EPS15-homology-domain-containing-protein-1 (EHD1) regulates traffic of cell surface receptors, including RTKs. We observed high frequency (67%) of EHD1 overexpression in 266 primary EWS patient tumor tissues, and Kaplan-Meier survival analysis of publicly available mRNA expression data showed that high EHD1 expression was associated with shorter patient survival. Objective/Question: This study aims to comprehend the underlying role of EHD1 in EWS oncogenesis. Experimental design and Results: In both dox-inducible EHD1-shRNA knockdown and EHD1-CRISPR-Cas9-knockout (KO) EWS cell line models(TC71, A673, and SKES1), we observed a significant impairment of in vitro oncogenic properties namely, cell proliferation, migration, invasion, soft-agar colony formation, and tumor-sphere formation, and the phenotypes were restored upon mouse-EHD1 rescue. Furthermore, by orthotopically implanting TC71 cells in the tibia of nude mice(xenograft model), we demonstrated a significant reduction in tumor size upon EHD1-depletion. Using a phospho-RTK profiling antibody array, we found reduced phospho-IGF-1R levels upon EHD1-KD, identifying IGF-1R as a potential target of regulation by EHD1. EHD1-KO reduced surface IGF-1R levels under steady-state and ligand-free conditions in EWS cells. IGF-1R and EHD1 were also found to colocalize intracellularly and co-immunoprecipitate after IGF-1 stimulation. Notably, EHD1-KO impaired the IGF-1R-mediated activation of downstream AKT and MAPK pathways. Mechanistically, EHD1 was shown to regulate traffic of newly synthesized IGF-1R and recycled pools from the Golgi to the cell surface, and in absence of EHD1, intracellular IGF-1R was shunted to the lysosome resulting in degradation. Finally, by dual targeting of EHD1 (genetic depletion) and IGF-1R (small-molecule-inhibitor Linsitinib), we observed an additive effect on inhibition of EWS cell proliferation and migration and upregulation of apoptosis. Conclusions: Our studies indicate a novel regulatory pathway of EHD1 requirement in IGF-1R cell surface display and sustaining IGF-1R-mediated oncogenesis in EWS. This highlights the prospects of therapeutic co-targeting of EHD1 and IGF-1R, thus enhancing IGF-1R targeted therapies in EWS.https://digitalcommons.unmc.edu/chri_forum/1040/thumbnail.jp

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

Measuring universal health coverage based on an index of effective coverage of health services in 204 countries and territories, 1990–2019 : A systematic analysis for the Global Burden of Disease Study 2019

Background Achieving universal health coverage (UHC) involves all people receiving the health services they need, of high quality, without experiencing financial hardship. Making progress towards UHC is a policy priority for both countries and global institutions, as highlighted by the agenda of the UN Sustainable Development Goals (SDGs) and WHO's Thirteenth General Programme of Work (GPW13). Measuring effective coverage at the health-system level is important for understanding whether health services are aligned with countries' health profiles and are of sufficient quality to produce health gains for populations of all ages. Methods Based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, we assessed UHC effective coverage for 204 countries and territories from 1990 to 2019. Drawing from a measurement framework developed through WHO's GPW13 consultation, we mapped 23 effective coverage indicators to a matrix representing health service types (eg, promotion, prevention, and treatment) and five population-age groups spanning from reproductive and newborn to older adults (≥65 years). Effective coverage indicators were based on intervention coverage or outcome-based measures such as mortality-to-incidence ratios to approximate access to quality care; outcome-based measures were transformed to values on a scale of 0–100 based on the 2·5th and 97·5th percentile of location-year values. We constructed the UHC effective coverage index by weighting each effective coverage indicator relative to its associated potential health gains, as measured by disability-adjusted life-years for each location-year and population-age group. For three tests of validity (content, known-groups, and convergent), UHC effective coverage index performance was generally better than that of other UHC service coverage indices from WHO (ie, the current metric for SDG indicator 3.8.1 on UHC service coverage), the World Bank, and GBD 2017. We quantified frontiers of UHC effective coverage performance on the basis of pooled health spending per capita, representing UHC effective coverage index levels achieved in 2019 relative to country-level government health spending, prepaid private expenditures, and development assistance for health. To assess current trajectories towards the GPW13 UHC billion target—1 billion more people benefiting from UHC by 2023—we estimated additional population equivalents with UHC effective coverage from 2018 to 2023. Findings Globally, performance on the UHC effective coverage index improved from 45·8 (95% uncertainty interval 44·2–47·5) in 1990 to 60·3 (58·7–61·9) in 2019, yet country-level UHC effective coverage in 2019 still spanned from 95 or higher in Japan and Iceland to lower than 25 in Somalia and the Central African Republic. Since 2010, sub-Saharan Africa showed accelerated gains on the UHC effective coverage index (at an average increase of 2·6% [1·9–3·3] per year up to 2019); by contrast, most other GBD super-regions had slowed rates of progress in 2010–2019 relative to 1990–2010. Many countries showed lagging performance on effective coverage indicators for non-communicable diseases relative to those for communicable diseases and maternal and child health, despite non-communicable diseases accounting for a greater proportion of potential health gains in 2019, suggesting that many health systems are not keeping pace with the rising non-communicable disease burden and associated population health needs. In 2019, the UHC effective coverage index was associated with pooled health spending per capita (r=0·79), although countries across the development spectrum had much lower UHC effective coverage than is potentially achievable relative to their health spending. Under maximum efficiency of translating health spending into UHC effective coverage performance, countries would need to reach $1398 pooled health spending per capita (US$ adjusted for purchasing power parity) in order to achieve 80 on the UHC effective coverage index. From 2018 to 2023, an estimated 388·9 million (358·6–421·3) more population equivalents would have UHC effective coverage, falling well short of the GPW13 target of 1 billion more people benefiting from UHC during this time. Current projections point to an estimated 3·1 billion (3·0–3·2) population equivalents still lacking UHC effective coverage in 2023, with nearly a third (968·1 million [903·5–1040·3]) residing in south Asia. Interpretation The present study demonstrates the utility of measuring effective coverage and its role in supporting improved health outcomes for all people—the ultimate goal of UHC and its achievement. Global ambitions to accelerate progress on UHC service coverage are increasingly unlikely unless concerted action on non-communicable diseases occurs and countries can better translate health spending into improved performance. Focusing on effective coverage and accounting for the world's evolving health needs lays the groundwork for better understanding how close—or how far—all populations are in benefiting from UHC