Cardiometabolic health after first pregnancy: Associations with social determinants of health. A nuMoM2b-HHS study.

Study objective: This study sought to evaluate the associations between social determinants of health (SDOH) at the time of first pregnancy and subsequent cardiometabolic health, defined as the development of metabolic syndrome. Design: nuMoM2b-HHS (Nulliparous Pregnancy Outcomes Study- Monitoring Mothers-to-Be-Heart Health Study) is an ongoing prospective cohort study. Setting: Eight academic medical centers enrolled and continue to follow participants. Participants: 4484 participants followed a mean of 3.2 years from the time of their first pregnancy. Interventions: N/a. Main outcome measure: Unadjusted and adjusted Poisson regression models with robust standard errors were used to obtain relative risks and 95% confidence intervals estimating the risk of metabolic syndrome for each baseline SDOH. In secondary analyses we examined the associations between SDOH and incident hypertension, obesity, and diabetes mellitus. Results: Metabolic syndrome developed in 13.6% of participants. Higher socioeconomic position at the time of pregnancy was associated with lower rates of metabolic syndrome [income > 200% poverty level aRR 0.55 (95% CI, 0.42-0.71), attainment of a bachelor's degree aRR 0.62 (0.46-0.84) or higher aRR 0.50 (0.35-0.71)], while being single [aRR 1.45 (95% CI, 1.18-1.77)] and having low health literacy were associated with a greater risk of metabolic syndrome [aRR 1.98 (95% CI, 1.28-3.07)]. Conclusions: Over a short interval following first pregnancy, participants accumulated high proportions of cardiovascular risk factors and metabolic syndrome, with some risk associated with SDOH. The impact of interventions addressing SDOH in pregnant people on cardiometabolic health should be tested as a means of reducing health inequities at the population level.

Examination of the short-range structure of molten salts: ThF4, UF4, and related alkali actinide fluoride systems.

The short-range structures of LiF-ThF4, NaF-AnF4, KF-AnF4, and Cs-AnF4 (An = Th, U), were probed using in situ high temperature Extended X-ray Absorption Fine Structure (EXAFS) spectroscopy. Signally, the EXAFS spectra of pure molten ThF4 and UF4 were measured for the first time. The data were interpreted with the aid of Molecular Dynamics (MD) and standard fitting of the EXAFS equation. As in related studies, a speciation distribution dominated by [AnFx]4-x (x = 7, 8, 9) coordination complexes was observed. The average coordination number was found to decrease with the increasing size of the alkali cation, and increase with AnF4 content. An average coordination number close to 6, which had not been detected before in melts of alkali actinide fluorides, was seen when CsF was used as solvent.

A feasibility study on the determination of 90Sr food-chain transfer using stable strontium as a surrogate and neutron activation analysis.

We evaluated the applicability of neutron activation analysis for investigating the potential mobility of 90Sr in a pasture area in Hungary. To measure strontium concentrations, we made use of the 84Sr(n,γ)85Sr radiative capture reaction using neutron activation analysis and performed gamma spectroscopy using Compton-suppression techniques on the resulting 514.0 keV gamma ray. Our values for soil-to-plant transfer factors value of 1.6 (2.2) kg kg-1 were in agreement with recommended values from the ICRP and IAEA, as well as similar studies performed by independent researchers. Our values for plant-to-animal transfer coefficients and concentration ratios varied from suggested values by several orders of magnitude to agreement with other values. Based on our results the utilized transfer of stable strontium could not be regarded as a convenient substitute to help clarify the long-term transfer of radioactive strontium in the environment, because short term dosing was applied. Neutron activation analysis provides a unique niche as a technique with very little chemical processing and short sample analysis times.

Flexible sample cell for real-time GISAXS, GIWAXS and XRR: design and construction.

Since the properties of functional materials are highly dependent on their specific structure, and since the structural changes, for example during crystallization, induced by coating and annealing processes are significant, the study of structure and its formation is of interest for fundamental and applied science. However, structure analysis is often limited to ex situ determination of final states due to the lack of specialized sample cells that enable real-time investigations. The lack of such cells is mainly due to their fairly complex design and geometrical restrictions defined by the beamline setups. To overcome this obstacle, an advanced sample cell has been designed and constructed; it combines automated doctor blading, solvent vapor annealing and sample hydration with real-time grazing-incidence wide- and small-angle scattering (GIWAXS/GISAXS) and X-ray reflectivity (XRR). The sample cell has limited spatial requirements and is therefore widely usable at beamlines and laboratory-scale instruments. The cell is fully automatized and remains portable, including the necessary electronics. In addition, the cell can be used by interested scientists in cooperation with the Institute for Crystallography and Structural Physics and is expandable with regard to optical secondary probes. Exemplary research studies are presented, in the form of coating of P3HT:PC61PM thin films, solvent vapor annealing of DRCN5T:PC71BM thin films, and hydration of supported phospholipid multilayers, to demonstrate the capabilities of the in situ cell.

Comparison of measured and simulated concentrations of 133Xe in the shallow subsurface.

Radioactive isotopes of the noble gases xenon and argon are considered primary indicators of an underground nuclear explosion. However, high atmospheric concentrations from other anthropogenic sources may lead to an elevation in the underground levels of these gases, particularly in times of increasing atmospheric pressure. In 2014, a week long sampling campaign near Canadian Nuclear Laboratories in the Ottawa River Valley resulted in first of their kind measurements of atmospheric 133Xe that had been pressed into the subsurface. In an effort to better understand this imprinting process, a second follow-up sampling campaign was conducted in the same location in 2016. The results of the second sampling campaign, where samples were collected at depths of 1 m and 2 m over a 14 day period and measured for their 133Xe concentration, are presented here. Gas transport and sample concentrations were predicted using the Subsurface Transport over Multiple Phases (STOMP) simulator. These results are examined and compared to the corresponding experimental results.

Xenon adsorption on geological media and implications for radionuclide signatures.

The detection of radioactive noble gases is a primary technology for verifying compliance with the pending Comprehensive Nuclear-Test-Ban Treaty. A fundamental challenge in applying this technology for detecting underground nuclear explosions is estimating the timing and magnitude of the radionuclide signatures. While the primary mechanism for transport is advective transport, either through barometric pumping or thermally driven advection, diffusive transport in the surrounding matrix also plays a secondary role. From the study of primordial noble gas signatures, it is known that xenon has a strong physical adsorption affinity in shale formations. Given the unselective nature of physical adsorption, isotherm measurements reported here show that non-trivial amounts of xenon adsorb on a variety of media, in addition to shale. A dual-porosity model is then discussed demonstrating that sorption amplifies the diffusive uptake of an adsorbing matrix from a fracture. This effect may reduce the radioxenon signature down to approximately one-tenth, similar to primordial xenon isotopic signatures.

The potential detection of low-level aerosol isotopes from new civilian nuclear processes.

As the world faces a challenging future in maintaining the commercial availability of radioactive isotopes for medical use, new methods of medical isotope production are being pursued. Many of these are small in size and could effectively operate continuously. With the potential for much shorter retention times, a new suite of isotopes may soon be found in the environment. The authors estimate that many more aerosols containing low-level isotopes of gas/volatile origin could be detectable at short range and times, and a few at longer ranges and times as compared to those released in more common nuclear reactor operations.

[Treatment of supine position-related obstructive sleep apnea with smartphone applications]. / Therapie rückenlagebezogener obstruktiver Schlafapnoe mittels Smartphone-App.

BACKGROUND: Positional obstructive sleep apnea (POSA) is common in mild and moderate forms of obstructive sleep apnea (OSA). Two smartphone applications (apps) professing to avoid the supine position (SP) are available: for Android the "Apnea Sleep Position Trainer" and for iOS the "SomnoPose-Sleep Position Monitor". The smartphone needs to be attached to the chest to recognize SP, which then triggers a vibration alarm. This is intended to encourage the patient to change position and the vibration stops as soon as SP is left. These apps, however, have not yet undergone a systematic evaluation. METHODS: Adult patients with polysomnographically diagnosed POSA were invited to participate in the study. POSA was defined as an apnea-hypopnea index (AHI) in SP >10, with AHI in a lateral position <10 and doubling of the AHI in SP. After 1 month, a control polysomnography (PSG) was performed and compliance (at least 4 h/night on 5 of 7 days) was evaluated after 6 months by phone. A sufficient therapy was defined as reduction in SP to <10% of the total sleep time and to an overall AHI <10. RESULTS: Although 57 patients entered the study, 24 did not appear to the PSG control; therefore, 33 patients finished the study, of whom 25 were treated successfully. The overall AHI in 33 patients was reduced from 14.5 ± 9.0 to 9.5 ± 12.6 and the time in SP decreased significantly from 71.1 ± 50.5 to 25.4 ± 65.0 min. Compliance among the 25 continuously treated patients after 6 months was 79.2%. CONCLUSION: Both smartphone apps have the capability to prevent PS in POSA patients and can potentially offer a cost-effective option in the treatment of POSA.

Calibration of the microcalorimeter spectrometer on-board the Hitomi (Astro-H) observatory (invited).

The Hitomi Soft X-ray Spectrometer (SXS) was a pioneering non-dispersive imaging x-ray spectrometer with 5 eV FWHM energy resolution, consisting of an array of 36 silicon-thermistor microcalorimeters at the focus of a high-throughput soft x-ray telescope. The instrument enabled astrophysical plasma diagnostics in the 0.3-12 keV band. We introduce the SXS calibration strategy and corresponding ground calibration measurements that took place from 2012-2015, including both the characterization of the microcalorimeter array and measurements of the x-ray transmission of optical blocking filters.

Identification of a haplotype associated with cholesterol deficiency and increased juvenile mortality in Holstein cattle.

Over the last decades, several genetic disorders have been discovered in cattle. However, the genetic background of disorders in calves is less reported. Recently, German cattle farmers reported on calves from specific matings with chronic diarrhea and retarded growth of unknown etiology. Affected calves did not respond to any medical treatment and died within the first months of life. These calves were underdeveloped in weight and showed progressive and severe emaciation despite of normal feed intake. Hallmark findings of the blood biochemical analysis were pronounced hypocholesterolemia and deficiency of fat-soluble vitamins. Results of the clinical and blood biochemical examination had striking similarities with findings reported in human hypobetalipoproteinemia. Postmortem examination revealed near-complete atrophy of the body fat reserves including the spinal canal and bone marrow. To identify the causal region, we performed a genome-wide association study with 9 affected and 21,077 control animals genotyped with the Illumina BovineSNP50 BeadChip (Illumina Inc., San Diego, CA), revealing a strong association signal on BTA 11. Subsequent autozygosity mapping identified a disease-associated haplotype encompassing 1.01 Mb. The segment of extended homozygosity contains 6 transcripts, among them the gene APOB, which is causal for cholesterol disorders in humans. However, results from multi-sample variant calling of 1 affected and 47 unaffected animals did not detect any putative causal mutation. The disease-associated haplotype has an important adverse effect on calf mortality in the homozygous state when comparing survival rates of risk matings vs. non-risk matings. Blood cholesterol values of animals are significantly associated with the carrier status indicating a codominant inheritance. The frequency of the haplotype in the current Holstein population was estimated to be 4.2%. This study describes the identification and phenotypic manifestation of a new Holstein haplotype characterized by pronounced hypocholesterolemia, chronic emaciation, growth retardation, and increased mortality in young cattle, denominated as cholesterol deficiency haplotype. Our genomic investigations and phenotypic examinations provide additional evidence for a mutation within the APOB gene causing cholesterol deficiency in Holstein cattle.

Drug therapy during pregnancy: implications for dental practice.

Pregnancy is accompanied by various physiological and physical changes, including those found in the cardiovascular, respiratory, gastrointestinal, renal and haematological systems. These alterations in the pregnant patient may potentially affect drug pharmacokinetics. Also, pharmacotherapy presents a unique matter due to the potential teratogenic effects of certain drugs. Although medications prescribed by dentists are generally safe during pregnancy, some modifications may be needed. In this article we will discuss the changes in the physiology during pregnancy and its impact on drug therapy. Specific emphasis will be given to the drugs commonly given by dentists, namely, local anaesthetics, analgesics, antibiotics and sedatives.

Implementation of a pharmacogenomics consult service to support the INGENIOUS trial.

Hospital systems increasingly utilize pharmacogenomic testing to inform clinical prescribing. Successful implementation efforts have been modeled at many academic centers. In contrast, this report provides insights into the formation of a pharmacogenomics consultation service at a safety-net hospital, which predominantly serves low-income, uninsured, and vulnerable populations. The report describes the INdiana GENomics Implementation: an Opportunity for the UnderServed (INGENIOUS) trial and addresses concerns of adjudication, credentialing, and funding.

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for UGT1A1 and Atazanavir Prescribing.

The antiretroviral protease inhibitor atazanavir inhibits hepatic uridine diphosphate glucuronosyltransferase (UGT) 1A1, thereby preventing the glucuronidation and elimination of bilirubin. Resultant indirect hyperbilirubinemia with jaundice can cause premature discontinuation of atazanavir. Risk for bilirubin-related discontinuation is highest among individuals who carry two UGT1A1 decreased function alleles (UGT1A1*28 or *37). We summarize published literature that supports this association and provide recommendations for atazanavir prescribing when UGT1A1 genotype is known (updates at www.pharmgkb.org).

Development of a low-level (37)Ar calibration standard.

Argon-37 is an environmental signature of an underground nuclear explosion. Producing and quantifying low-level (37)Ar standards is an important step in the development of sensitive field measurement instruments. This paper describes progress at Pacific Northwest National Laboratory in developing a process to generate and quantify low-level (37)Ar standards, which can be used to calibrate sensitive field systems at activities consistent with soil background levels. This paper presents a discussion of the measurement analysis, along with assumptions and uncertainty estimates.

The diverse environmental burden of city-scale urban water systems.

Recent years have seen an increase in the use of Life Cycle Assessment (LCA) to inform urban water systems research. The attraction of LCA is its capacity to identify trade-offs across a broad range of environmental issues and a broad range of technologies. However, without some additional perspective on the scale of the results, prioritisation of these concerns will remain difficult. LCA studies at the whole-of-system level are required to identify the diversity of life cycle environmental burdens associated with urban water systems, and the main contributors to these impacts. In this study, environmental impact profiles were generated for two city-scale urban water systems: one typical of many urban centres, with a high reliance on freshwater extraction and the majority of treated wastewater being discharged to the sea; and one that adopts a more diverse range of water supply and wastewater recycling technologies. The profiles were based on measured data for most system components, otherwise best available empirical data from the literature. Impact models were chosen considering the substantial methodological developments that have occurred in recent years. System operations, directly within the sphere of influence of water system managers, play the dominant role in all but one of the 14 life cycle impact categories considered. While energy use is the main cause of changes in the impact profiles when the alternative water supply technologies are included, it is not the only important driver of impacts associated with city-scale urban water systems. Also extremely important are process emissions related to wastewater treatment and dams (notably fugitive gases, wastewater discharges, and biosolids disposal). The results clearly indicate a diverse range of environmental impacts of relevance, extending beyond the traditional concerns of water use and nutrient discharge. Neither energy use, nor greenhouse gas footprints, are likely to be an adequate proxy for representing these additional concerns. However, methodological improvements will be required for certain LCA impact models to support future case study analysis, as will a comprehensive critique of the implications from selecting different impact models.

LC-MS/MS-based quantification of cholesterol and related metabolites in dried blood for the screening of inborn errors of sterol metabolism.

Smith-Lemli-Opitz syndrome (SLOS) is an inherited metabolic disease in the cholesterol biosynthesis pathway which is characterised by accumulation of 7- and 8-dehydrocholesterol and by reduced cholesterol concentrations in all tissues and body fluids. With this study, we developed a new, rapid, robust and high-throughput tandem mass spectrometric method as routine application for the selective SLOS screening and therapy monitoring in serum and dried blood. After protein precipitation of 10 µL serum or 4.7 mm dried blood spot, the sum of 7- and 8-dehydrocholesterol (DHC) was analysed by rapid chromatography combined with tandem mass spectrometry. Method comparison with GC-MS was performed for 46 serum samples. A comparison between serum and corresponding dried blood spots for DHC and cholesterol was performed with 40 samples from SLOS patients. Concentrations of DHC and cholesterol were analysed in 2 dried blood samples from newborns with SLOS and 100 unaffected newborns. Intra- and inter-assay variabilities ranged between 3.7 and 17.7% for serum and dried blood spots. Significant correlations between the new LC-MS/MS method and GC-MS were determined for DHC (r = 0.937, p < 0.001) and for cholesterol (r = 0.946, p < 0.001). Significant coefficients of correlation between serum and dried blood spot samples above 0.8 were calculated for both analytes. A cut-off value of 5.95 for the ratio of DHC/cholesterol (multiplied by 1000) was found to distinguish newborns diagnosed with SLOS from normal newborns in a retrospective analysis after 5 years. The developed method enables a rapid quantification of the sum parameter 7- and 8-DHC in newborns and SLOS patients under therapy in serum as well as dried blood spot samples.

Chronic villitis of unknown etiology and massive chronic intervillositis have similar immune cell composition.

INTRODUCTION: Chronic villitis of unknown etiology (CVUE) and massive chronic intervillositis (MCI) are placental lesions associated with infiltration of mononuclear cells in the chorionic villi and the intervillous spaces, respectively. It is not well known whether immune cells in CVUE and MCI have similar phenotypic characteristics. METHODS: A cross-sectional study of third trimester placentas was conducted to identify immune cell subpopulations in CVUE and MCI (n = 17/group). CVUE was diagnosed with H&E staining and antibody to CD3 in serial sections; and MCI, by the presence of massive infiltration of mononuclear cells in the intervillous spaces. Immune cells, ICAM-1 expression and nuclear factor κB (NF-κB) activation were determined immunohistochemically. RESULTS: CVUE and MCI showed similar infiltrates, mainly CD68+ and CD3+ cells. Most cells (>80%) were CD45RB+, and one third were CD45RO+ in both lesions. There were slightly more CD8+ than CD4+ cells in both CVUE and MCI. More than 90% of cells in CVUE and MCI were ICAM-1+ with NFκB nuclear localization. Syncytiotrophoblast ICAM-1 expression was significantly (p < 0.001) higher in MCI (mean of 81.0; range of 71.6-86.0) than in CVUE (52.4; 36.4-59.4) or normal placentas (0.2; 0.0-0.6). Both, failure of physiologic transformation of spiral arteries and placental atherosclerosis-like lesions of atherosis were significantly more frequent in MCI than in CVUE or normal placentas (p = 0.044 and p = 0.007, respectively). DISCUSSION: These finding suggest that MCI and CVUE have very similar infiltration of immune cells although MCI has more severe placental lesions.