Validity of predictive equations for 24-h urinary sodium excretion in adults aged 18–39 y1–5

Background: Collecting a 24-h urine sample is recommended for monitoring the mean population sodium intake, but implementation can be difficult. Objective: The objective was to assess the validity of published equations by using spot urinary sodium concentrations to predict 24-h sodium excretion. Design: This was a cross-sectional study, conducted from June to August 2011 in metropolitan Washington, DC, of 407 adults aged 18–39 y, 48% black, who collected each urine void in a separate container for 24 h. Four timed voids (morning, afternoon, evening, and overnight) were selected from each 24-h collection. Published equations were used to predict 24-h sodium excretion with spot urine by specimen timing and race-sex subgroups. We examined mean differences with measured 24-h sodium excretion (bias) and individual differences with the use of Bland-Altman plots. Results: Across equations and specimens, mean bias in predicting 24-h sodium excretion for all participants ranged from2267 to 1300mg (Kawasaki equation). Bias was least with International Cooperative Study on Salt, Other Factors, and Blood Pressure (INTERSALT) equations with morning (2165 mg; 95% CI: 2295, 36 mg), afternoon (290 mg; 2208, 28 mg), and evening (2120 mg; 2230, 211 mg) specimens. With overnight specimens, mean bias was least when the Tanaka (223 mg; 95% CI: 2141, 95 mg) or Mage (2145 mg; 2314, 25 mg) equations were used but was statistically significant when using the Tanaka equations among females (216 to 243 mg) and the Mage equations among races other than black (2554 to 2372 mg). Significant over- and underprediction occurred across individual sodium excretion concentrations. Conclusions: Using a single spot urine, INTERSALT equations may provide the least biased information about population mean sodium intakes among young US adults. None of the equations evaluated provided unbiased estimates of individual 24-h sodium excretion. This trial was registered at clinicaltrials.gov as NCT01631240

Shale Oil Value Enhancement Research. Quarterly Report, March 1 - May 31, 1996

The overall objective is to develop a new technology for manufacturing valuable marketable products from shale oil. Phase I objectives are to identify desirable components in shale oil, develop separations techniques for those components, identify market needs and to identify plausible products manufacturable from raw shale oil to meet those needs. The quarter`s efforts were concentrated on (a) compound type analysis of shale oil and its extraction products, (b) thermal hydrodealkylation of the >290{degrees}C polar fraction, (c) reaction of pyridinic type compounds to form secondary products, (d) updating SPX economic analysis, and (e) preparation of a business plan for presentation before the Dawnbreaker Commercial Assistance Program. The subcontract on the thermal hydrodealkylation work at the University of Utah ended at May 3 1, 1996. We have obtained valuable information from the batch experiments. The progress on the flow reactor proved somewhat limited because of the restriction of the existing reactor configuration. The liaison with potential industrial partners is continuing. An additional company has reached agreement to proceed with a geochemical testing of shale oil derived products

Shale Oil Value Enhancement Research. Quarterly Report, June 1 - August 31, 1996

The overall objective is to develop a new technology for manufacturing valuable marketable products from shale oil. The quarter`s efforts were concentrated on (a) THDA and reaction of alkylpyridines at elevated conditions, (b) compound type analysis of kerogen oil and its derived products, (b) thermal hydrodealkylation of the > 290{degrees}C polar fraction, (c) secondary reactions of pyridinic type compounds to form marketable products, and (d) preparation of presentation to the Dawnbreaker Commercial Assistance Program. Excellent progress is being made in all cases. Our market analysis and industrial feedback indicate that the low molecular weight pyridines are the main market driving force. We are concentrating our effort toward increasing the yield of ``light`` pyridines before the end of Phase II(a). Our current laboratory set-up can only produce analytical quantity of samples, which is not sufficient for marketing purpose. However, the completion of a secondary flow THDA unit for a pilot-scale production depends on the availability of the Phase-II(b) and Phase-III funding

Shale Oil Value Enhancement Research. Quarterly Report, September 1 - November 30, 1995

Activities during this quarter focused on compound type analysis of shale oil extraction products and improvement of the continuous extraction process. We have installed a walk-in fume hood to improve the ventilation of our working environment while handling of larger amounts of shale oil and volatile solvents in our Phase-II(a) work. The fume hood accommodates the distillation column, rotary evaporator, and the CLLX column. During the construction period, experimental work was carried on at a smaller scale. Modifications to the thermal hydrodealkylation process unit at the University of Utah have been completed. The higher boiling polar fraction of shale oil was fed and the preliminary ran showed promising results. The search for potential industrial partners is continuing. During this period, the prijcipal investigator has visited six industrial companies that are candidates for partner/buyer relationship. Currently, we are pursuing confidentiality agreements with four of them. It is the intent to focus our research toward addressing the objectives of those companies who show sufficient interest in the shale oil value enhancement project to enter the next level of discussions

Phenotypic screening identifies a trisubstituted imidazo[1,2-a]pyridine series that induces differentiation in multiple AML cell lines

Acute myeloid leukaemia (AML) is an aggressive type of leukaemia with low rates of long-term survival. While the current standard of care is based on cytotoxic chemotherapy, a promising emerging approach is differentiation therapy. However, most current differentiating agents target specific mutations and are effective only in certain patient subtypes. To identify agents which may be effective in wider population cohorts, we performed a phenotypic screen with the myeloid marker CD11b and identified a compound series that was able to differentiate AML cell lines in vitro regardless of their mutation status. Structure-activity relationship studies revealed that replacing the formamide and catechol methyl ether groups with sulfonamide and indazole respectively improved the in vitro metabolic profile of the series while maintaining the differentiation profile in multiple cell lines. This optimisation exercise enabled progression of a lead compound to in vivo efficacy testing. Our work supports the promise of phenotypic screening to identify novel small molecules that induce differentiation in a wide range of AML subtypes

Enhanced NFκB and AP-1 transcriptional activity associated with antiestrogen resistant breast cancer

BACKGROUND: Signaling pathways that converge on two different transcription factor complexes, NFκB and AP-1, have been identified in estrogen receptor (ER)-positive breast cancers resistant to the antiestrogen, tamoxifen. METHODS: Two cell line models of tamoxifen-resistant ER-positive breast cancer, MCF7/HER2 and BT474, showing increased AP-1 and NFκB DNA-binding and transcriptional activities, were studied to compare tamoxifen effects on NFκB and AP-1 regulated reporter genes relative to tamoxifen-sensitive MCF7 cells. The model cell lines were treated with the IKK inhibitor parthenolide (PA) or the proteasome inhibitor bortezomib (PS341), alone and in combination with tamoxifen. Expression microarray data available from 54 UCSF node-negative ER-positive breast cancer cases with known clinical outcome were used to search for potential genes signifying upregulated NFκB and AP-1 transcriptional activity in association with tamoxifen resistance. The association of these genes with patient outcome was further evaluated using node-negative ER-positive breast cancer cases identified from three other published data sets (Rotterdam, n = 209; Amsterdam, n = 68; Basel, n = 108), each having different patient age and adjuvant tamoxifen treatment characteristics. RESULTS: Doses of parthenolide and bortezomib capable of sensitizing the two endocrine resistant breast cancer models to tamoxifen were capable of suppressing NFκB and AP-1 regulated gene expression in combination with tamoxifen and also increased ER recruitment of the transcriptional co-repressor, NCoR. Transcript profiles from the UCSF breast cancer cases revealed three NFκB and AP-1 upregulated genes – cyclin D1, uPA and VEGF – capable of dichotomizing node-negative ER-positive cases into early and late relapsing subsets despite adjuvant tamoxfien therapy and most prognostic for younger age cases. Across the four independent sets of node-negative ER-positive breast cancer cases (UCSF, Rotterdam, Amsterdam, Basel), high expression of all three NFκB and AP-1 upregulated genes was associated with earliest metastatic relapse. CONCLUSION: Altogether, these findings implicate increased NFκB and AP-1 transcriptional responses with tamoxifen resistant breast cancer and early metastatic relapse, especially in younger patients. These findings also suggest that agents capable of preventing NFκB and AP-1 gene activation may prove useful in restoring the endocrine responsiveness of such high-risk ER-positive breast cancers

Global investments in pandemic preparedness and COVID-19: development assistance and domestic spending on health between 1990 and 2026

Background The COVID-19 pandemic highlighted gaps in health surveillance systems, disease prevention, and treatment globally. Among the many factors that might have led to these gaps is the issue of the financing of national health systems, especially in low-income and middle-income countries (LMICs), as well as a robust global system for pandemic preparedness. We aimed to provide a comparative assessment of global health spending at the onset of the pandemic; characterise the amount of development assistance for pandemic preparedness and response disbursed in the first 2 years of the COVID-19 pandemic; and examine expectations for future health spending and put into context the expected need for investment in pandemic preparedness. Methods In this analysis of global health spending between 1990 and 2021, and prediction from 2021 to 2026, we estimated four sources of health spending: development assistance for health (DAH), government spending, out-of-pocket spending, and prepaid private spending across 204 countries and territories. We used the Organisation for Economic Co-operation and Development (OECD)'s Creditor Reporting System (CRS) and the WHO Global Health Expenditure Database (GHED) to estimate spending. We estimated development assistance for general health, COVID-19 response, and pandemic preparedness and response using a keyword search. Health spending estimates were combined with estimates of resources needed for pandemic prevention and preparedness to analyse future health spending patterns, relative to need. Findings In 2019, at the onset of the COVID-19 pandemic, US$9·2 trillion (95$7·3 trillion (95% UI 7·2–7·4) in 2019; 293·7 times the $24·8 billion (95$43·1 billion in development assistance was provided to maintain or improve health. The pandemic led to an unprecedented increase in development assistance targeted towards health; in 2020 and 2021, $1·8 billion in DAH contributions was provided towards pandemic preparedness in LMICs, and$37·8 billion was provided for the health-related COVID-19 response. Although the support for pandemic preparedness is 12·2% of the recommended target by the High-Level Independent Panel (HLIP), the support provided for the health-related COVID-19 response is 252·2% of the recommended target. Additionally, projected spending estimates suggest that between 2022 and 2026, governments in 17 (95% UI 11–21) of the 137 LMICs will observe an increase in national government health spending equivalent to an addition of 1% of GDP, as recommended by the HLIP. Interpretation There was an unprecedented scale-up in DAH in 2020 and 2021. We have a unique opportunity at this time to sustain funding for crucial global health functions, including pandemic preparedness. However, historical patterns of underfunding of pandemic preparedness suggest that deliberate effort must be made to ensure funding is maintained

Tracking development assistance for health and for COVID-19: a review of development assistance, government, out-of-pocket, and other private spending on health for 204 countries and territories, 1990-2050

Background The rapid spread of COVID-19 renewed the focus on how health systems across the globe are financed, especially during public health emergencies. Development assistance is an important source of health financing in many low-income countries, yet little is known about how much of this funding was disbursed for COVID-19. We aimed to put development assistance for health for COVID-19 in the context of broader trends in global health financing, and to estimate total health spending from 1995 to 2050 and development assistance for COVID-19 in 2020. Methods We estimated domestic health spending and development assistance for health to generate total health-sector spending estimates for 204 countries and territories. We leveraged data from the WHO Global Health Expenditure Database to produce estimates of domestic health spending. To generate estimates for development assistance for health, we relied on project-level disbursement data from the major international development agencies' online databases and annual financial statements and reports for information on income sources. To adjust our estimates for 2020 to include disbursements related to COVID-19, we extracted project data on commitments and disbursements from a broader set of databases (because not all of the data sources used to estimate the historical series extend to 2020), including the UN Office of Humanitarian Assistance Financial Tracking Service and the International Aid Transparency Initiative. We reported all the historic and future spending estimates in inflation-adjusted 2020 US$, 2020 US$ per capita, purchasing-power parity-adjusted US$per capita, and as a proportion of gross domestic product. We used various models to generate future health spending to 2050. Findings In 2019, health spending globally reached$8. 8 trillion (95% uncertainty interval UI] 8.7-8.8) or $1132 (1119-1143) per person. Spending on health varied within and across income groups and geographical regions. Of this total,$40.4 billion (0.5%, 95% UI 0.5-0.5) was development assistance for health provided to low-income and middle-income countries, which made up 24.6% (UI 24.0-25.1) of total spending in low-income countries. We estimate that $54.8 billion in development assistance for health was disbursed in 2020. Of this,$13.7 billion was targeted toward the COVID-19 health response. $12.3 billion was newly committed and$1.4 billion was repurposed from existing health projects. $3.1 billion (22.4$2.4 billion (17.9%) was for supply chain and logistics. Only $714.4 million (7.7$1519 (1448-1591) per person in 2050, although spending across countries is expected to remain varied. Interpretation Global health spending is expected to continue to grow, but remain unequally distributed between countries. We estimate that development organisations substantially increased the amount of development assistance for health provided in 2020. Continued efforts are needed to raise sufficient resources to mitigate the pandemic for the most vulnerable, and to help curtail the pandemic for all. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd

KEROGEN OIL VALUE ENHANCEMENT RESEARCH

Task 13 (a) was approved on December 21, 2001. Minimal work was performed for the quarter during the approval process. Laboratory and equipment facilities have been maintained in anticipation of the work to be done. The PI communicated with DOE and Estonia researchers during this period, providing advice and direction for the startup of the Estonia research, and preparing a Draft Teaming Agreement. The PI participated in an industrial liaison meeting with DOE personnel. This meeting is expected to lead to formal cooperation between industry and government