Integrated high performance microfluidic organic analysis instrument for planetary and space exploration.

The exploration of our solar system to characterize the molecular organic inventory will enable the identification of potentially habitable regions and initiate the search for biosignatures of extraterrestrial life. However, it is challenging to perform the required high-resolution, high-sensitivity chemical analyses in space and in planetary environments. To address this challenge, we have developed a microfluidic organic analyzer (MOA) instrument that consists of a multilayer programmable microfluidic analyzer (PMA) for fluidic processing at the microliter scale coupled with a microfabricated glass capillary electrophoresis (CE) wafer for separation and analysis of the sample components. Organic analytes are labeled with a functional group-specific (e.g. amine, organic acid, aldehyde) fluorescent dye, separated according to charge and hydrodynamic size by capillary electrophoresis (CE), and detected with picomolar limit of detection (LOD) using laser-induced fluorescence (LIF). Our goal is a sensitive automated instrument and autonomous process that enables sample-in to data-out performance in a flight capable format. We present here the design, fabrication, and operation of a technology development unit (TDU) that meets these design goals with a core mass of 3 kg and a volume of <5 L. MOA has a demonstrated resolution of 2 × 105 theoretical plates for relevant amino acids using a 15 cm long CE channel and 467 V cm-1. The LOD of LIF surpasses 100 pM (0.01 ppb), enabling biosignature detection in harsh environments on Earth. MOA is ideally suited for probing biosignatures in potentially habitable destinations on icy moons such as Europa and Enceladus, and on Mars.

What will the cardiovascular disease slowdown cost? Modelling the impact of CVD trends on dementia, disability, and economic costs in England and Wales from 2020-2029.

BACKGROUND: There is uncertainty around the health impact and economic costs of the recent slowing of the historical decline in cardiovascular disease (CVD) incidence and the future impact on dementia and disability. METHODS: Previously validated IMPACT Better Ageing Markov model for England and Wales, integrating English Longitudinal Study of Ageing (ELSA) data for 17,906 ELSA participants followed from 1998 to 2012, linked to NHS Hospital Episode Statistics. Counterfactual design comparing two scenarios: Scenario 1. CVD Plateau-age-specific CVD incidence remains at 2011 levels, thus continuing recent trends. Scenario 2. CVD Fall-age-specific CVD incidence goes on declining, following longer-term trends. The main outcome measures were age-related healthcare costs, social care costs, opportunity costs of informal care, and quality adjusted life years (valued at £60,000 per QALY). FINDINGS: The total 10 year cumulative incremental net monetary cost associated with a persistent plateauing of CVD would be approximately £54 billion (95% uncertainty interval £14.3-£96.2 billion), made up of some £13 billion (£8.8-£16.7 billion) healthcare costs, £1.5 billion (-£0.9-£4.0 billion) social care costs, £8 billion (£3.4-£12.8 billion) informal care and £32 billion (£0.3-£67.6 billion) value of lost QALYs. INTERPRETATION: After previous, dramatic falls, CVD incidence has recently plateaued. That slowdown could substantially increase health and social care costs over the next ten years. Healthcare costs are likely to increase more than social care costs in absolute terms, but social care costs will increase more in relative terms. Given the links between COVID-19 and cardiovascular health, effective cardiovascular prevention policies need to be revitalised urgently.

Dementia and disadvantage in the USA and England: population-based comparative study.

OBJECTIVES: To compare dementia prevalence and how it varies by socioeconomic status (SES) across the USA and England. DESIGN: Population-based comparative study. SETTING: Non-Hispanic whites aged over 70 population in the USA and England. PARTICIPANTS: Data from the Health and Retirement Study and the English Longitudinal Study of Ageing, which are harmonised, nationally representative panel studies. The sample includes 5330 and 3147 individuals in the USA and England, respectively. MAIN OUTCOME MEASURES: Between country differences in age-gender standardised dementia prevalence, across the SES gradient. Dementia prevalence was estimated in each country using an algorithm based on an identical battery of demographic, cognitive and functional measures. RESULTS: Dementia prevalence is higher among the disadvantaged in both countries, with the USA being more unequal according to four measures of SES. Overall prevalence was lower in England at 9.7% (95% CI 8.9% to 10.6%) than the USA at 11.2% (95% CI 10.6% to 11.8%), a difference of 1.4 percentage points (pp) (p=0.0055). Most of the between country difference is driven by the bottom of the SES distribution. In the lowest income decile individuals in the USA had 7.3 pp (p<0.0001) higher prevalence than in England. Once past health factors and education were controlled for, most of the within country inequalities disappeared; however, the cross-country difference in prevalence for those in lowest income decile remained disproportionately high. CONCLUSIONS: There is inequality in dementia prevalence according to income, wealth and education in both the USA and England. England has lower dementia prevalence and a less steep SES gradient. Most of the cross-country difference is concentrated in the lowest SES group, which provides evidence that disadvantage in the USA is a disproportionately high risk factor for dementia.

Fabrication of high-quality glass microfluidic devices for bioanalytical and space flight applications.

Microfabricated glass microfluidic and Capillary Electrophoresis (CE) devices have been utilized in a wide variety of applications over the past thirty years. At the Berkeley Space Sciences Laboratory, we are working to further expand this technology by developing analytical instruments to chemically explore our solar system. This effort requires improving the quality and reliability of glass microfabrication through quality control procedures at every stage of design and manufacture. This manuscript provides detailed information on microfabrication technology for the production of high-quality glass microfluidic chips in compliance with industrial standards and space flight instrumentation quality control.•The methodological protocol provided in this paper includes the scope of each step of the manufacturing process, materials and technologies recommended and the specific challenges that often confront the process developer.•Types and sources of fabrication error at every stage have been identified and their solutions have been proposed and verified.•We present robust and rigorous manufacturing and quality control procedures that will assist other researchers in achieving the highest possible quality glass microdevices using the latest apparatus in a routine and reliable fashion.

End-Of-Life Medical Spending In Last Twelve Months Of Life Is Lower Than Previously Reported.

Although end-of-life medical spending is often viewed as a major component of aggregate medical expenditure, accurate measures of this type of medical spending are scarce. We used detailed health care data for the period 2009-11 from Denmark, England, France, Germany, Japan, the Netherlands, Taiwan, the United States, and the Canadian province of Quebec to measure the composition and magnitude of medical spending in the three years before death. In all nine countries, medical spending at the end of life was high relative to spending at other ages. Spending during the last twelve months of life made up a modest share of aggregate spending, ranging from 8.5 percent in the United States to 11.2 percent in Taiwan, but spending in the last three calendar years of life reached 24.5 percent in Taiwan. This suggests that high aggregate medical spending is due not to last-ditch efforts to save lives but to spending on people with chronic conditions, which are associated with shorter life expectancies.

The Accuracy of Economic Measurement in the Health and Retirement Study.

We assess the quality of the HRS's measures of out-of-pocket medical spending and health insurance premia, both in the "core interviews" and in the "exit interview" data. We provide detailed evidence on the quality of the HRS insurance premia data, and we compare the HRS exit data to exit data in the MCBS. We document how changes in survey questions, including the introduction of "unfolding brackets," affect the HRS measures. We document what we believe are errors in the HRS imputations and provide some suggestions for improving the accuracy of some imputed variables. Overall, we find the HRS data to be of high quality. However, we believe that many interesting variables in the HRS are under-utilized because users must perform imputations themselves.

Design and Performance of the ICON EUV Spectrograph.

We present the design, implementation, and on-ground performance measurements of the Ionospheric Connection Explorer EUV spectrometer, ICON EUV, a wide field (17° x 12°) extreme ultraviolet (EUV) imaging spectrograph designed to observe the lower ionosphere at tangent altitudes between 100 and 500 km. The primary targets of the spectrometer, which has a spectral range of 54-88 nm, are the Oil emission lines at 61.6 nm and 83.4 nm. Its design, using a single optical element, permits a 0°.26 imaging resolution perpendicular to the spectral dispersion direction with a large (12°) acceptance parallel to the dispersion direction while providing a slit-width dominated spectral resolution of R ~ 25 at 58.4 nm. Pre-flight calibration shows that the instrument has met all of the science performance requirements.

Medical Spending of the US Elderly.

We use data from the Medicare Current Beneficiary Survey (MCBS) to document the medical spending of Americans aged 65 and older. We find that medical expenses more than double between ages 70 and 90 and that they are very concentrated: the top 10 per cent of all spenders are responsible for 52 per cent of medical spending in a given year. In addition, those currently experiencing either very low or very high medical expenses are likely to find themselves in the same position in the future. We also find that the poor consume more medical goods and services than the rich and have a much larger share of their expenses covered by the government. Overall, the government pays for over 65 per cent of the elderly's medical expenses. Despite this, the expenses that remain after government transfers are even more concentrated among a small group of people. Thus, government health insurance, while potentially very valuable, is far from complete. Finally, while medical expenses before death can be large, on average they constitute only a small fraction of total spending, both in the aggregate and over the life cycle. Hence, medical expenses before death do not appear to be an important driver of the high and increasing medical spending found in the US.

Herpes zoster and exposure to the varicella zoster virus in an era of varicella vaccination.

OBJECTIVES: We performed a case-control study to determine if participants with herpes zoster had fewer contacts with persons with varicella or zoster, and with young children, to explore the hypothesis that exposure to persons with varicella zoster virus (VZV) results in "immune boosting." METHODS: Participants were patients of the multispecialty Marshfield Clinic in Wisconsin. We identified patients aged 40 to 79 years with a new diagnosis of zoster from August 2000 to July 2005. We frequency matched control participants to case participants for age. We confirmed diagnoses by chart review and assessed exposures by interview. RESULTS: Interviews were completed by 633 of 902 eligible case participants (70.2%) and 655 of 1149 control participants (57.0%). The number of varicella contacts was not associated with zoster; there was no trend even at the highest exposure level (3 or more contacts). Similarly, there was no association with exposure to persons with zoster or to children, or with workplace exposures. CONCLUSIONS: Although exposure to VZV in our study was relatively low, the absence of a relationship with zoster reflects the uncertain influence of varicella circulation on zoster epidemiology.

Varicella vaccination and ischemic stroke in children: is there an association?

BACKGROUND: Ischemic stroke is a known complication of varicella disease. Although there have been case reports of ischemic stroke after varicella vaccination, the existence and magnitude of any vaccine-associated risk has not been determined. OBJECTIVE. The purpose of this work was to determine whether varicella vaccination is associated with an increased risk of ischemic stroke and encephalitis in children within 12 months after vaccination. PATIENTS AND METHODS: We conducted a retrospective cohort study based on computerized data from children 11 months through 17 years old enrolled for > or =12 months in the Vaccine Safety DataLink from 1991 through 2004. International Classification of Disease codes identified cases of ischemic stroke (433-436, 437.1, 437.4, 437.6, 437.8-437.9) and encephalitis (052.0, 323.5, 323.8-9). Cox regression was used to model the risk in the 12 months after vaccination relative to all other person-time. Covariates included calendar time, gender, and stroke risk factors (eg, sickle cell disease). RESULTS: Varicella vaccine was administered to 35.3% of the 3.2 million children in the cohort. There were 203 new inpatient ischemic stroke diagnoses, including 8 that occurred within 12 months after vaccination; there was no temporal clustering. The adjusted stroke hazard ratio was not elevated during any of the time periods in the 12 months after vaccination. Stroke was strongly associated with known risk factors such as sickle cell disease and cardiac disease. None of the 243 encephalitis cases occurred during the first 30 days after vaccination, and there was no association between encephalitis and varicella vaccination at any time in the 12 months after vaccination. CONCLUSION: Our retrospective cohort study of >3 million children found no association between varicella vaccine and ischemic stroke.