Publications

This paper describes the formation of nanometer-scale features in gold and silicon substrates. The features in gold were made by using a self-assembled monolayer (SAM) of nonanethiolate on gold as a resist damaged by neutral cesium atoms. A SAM resist of octyltrichlorosilane on silicon dioxide was used as a resist sensitive to cesium atoms in order to fabricate features in silicon. A silicon nitride membrane perforated with nm- and micrometers -scale holes was used to pattern the atomic beam. Etching transferred the pattern formed in the SAM layer into the underlying substrate. Features of < 100-nm size were etched into the gold and silicon substrates. Investigations of the reflectivity of samples of nonanethiolate on gold, exposed to the atomic beam without a mask and subsequently etched, revealed that the resist-etch system exhibited a minimum threshold dose of cesium for damage; at doses lower than approximately 3 monolayers, the damage was insufficient to allow penetration of the SAM by the etching solution. The threshold dose for damage of the octyltrichlorosilane SAM on silicon dioxide is under investigation.

The use of expensive infertility treatments is increasing rapidly. To compare the prenatal and neonatal health care costs after IVF and spontaneous conception, we conducted a study based on a cohort of IVF and control pregnancies and neonates.A cohort of 215 IVF mothers and 255 IVF neonates were compared with a cohort of 662 control mothers and 388 control children, randomly chosen from the Finnish Medical Birth Register and matched for sex, year of birth, area of residence, parity, maternal age, socioeconomic status and plurality. The analyses on prenatal and neonatal costs were performed by plurality. Singletons were also compared with twins. The cost calculations were based on the known level of utilization of maternal and neonatal health care services.The total health care costs for an IVF singleton until the end of the neonatal period were 5780 and 15 580 for an IVF twin. The health care costs were 1.3-fold for IVF singletons and 1.1-fold for IVF twins compared to control singletons and twins. The costs for twins were approximately 3-fold compared to singletons.The health care costs of an IVF singleton neonate were higher than those of a spontaneously conceived control neonate with similar backgrounds. For twins the health care costs were equal. Multiple births increase the health care costs and therefore the reduction of multiple pregnancies is the most effective way to reduce the health care costs resulting from IVF.

High alcohol consumption is a major cause of morbidity, yet alcohol is associated with both favourable and adverse effects on cardiometabolic risk markers. We aimed to characterize the associations of usual alcohol consumption with a comprehensive systemic metabolite profile in young adults.Cross-sectional associations of alcohol intake with 86 metabolic measures were assessed for 9778 individuals from three population-based cohorts from Finland (age 24-45 years, 52% women). Metabolic changes associated with change in alcohol intake during 6-year follow-up were further examined for 1466 individuals. Alcohol intake was assessed by questionnaires. Circulating lipids, fatty acids and metabolites were quantified by high-throughput nuclear magnetic resonance metabolomics and biochemical assays.Increased alcohol intake was associated with cardiometabolic risk markers across multiple metabolic pathways, including higher lipid concentrations in HDL subclasses and smaller LDL particle size, increased proportions of monounsaturated fatty acids and decreased proportion of omega-6 fatty acids, lower concentrations of glutamine and citrate (P < 0.001 for 56 metabolic measures). Many metabolic biomarkers displayed U-shaped associations with alcohol consumption. Results were coherent for men and women, consistent across the three cohorts and similar if adjusting for body mass index, smoking and physical activity. The metabolic changes accompanying change in alcohol intake during follow-up resembled the cross-sectional association pattern (R2 = 0.83, slope = 0.72 ± 0.04).Alcohol consumption is associated with a complex metabolic signature, including aberrations in multiple biomarkers for elevated cardiometabolic risk. The metabolic signature tracks with long-term changes in alcohol consumption. These results elucidate the double-edged effects of alcohol on cardiovascular risk.

In epidemiological studies, samples are often collected long before disease onset or outcome assessment. Understanding the long-term stability of biomarkers measured in these samples is crucial. We estimated within-person stability over 10 years of metabolites and metabolite features (n = 5938) in the Nurses’ Health Study (NHS): the primary dataset included 1880 women with 1184 repeated samples donated 10 years apart while the secondary dataset included 1456 women with 488 repeated samples donated 10 years apart. We quantified plasma metabolomics using two liquid chromatography mass spectrometry platforms (lipids and polar metabolites) at the Broad Institute (Cambridge, MA, USA). Intra-class correlations (ICC) were used to estimate long-term (10 years) within-person stability of metabolites and were calculated as the proportion of the total variability (within-person + between-person) attributable to between-person variability. Within-person variability was estimated among participants who donated two blood samples approximately 10 years apart while between-person variability was estimated among all participants. In the primary dataset, the median ICC was 0.43 (1st quartile (Q1): 0.36; 3rd quartile (Q3): 0.50) among known metabolites and 0.41 (Q1: 0.34; Q3: 0.48) among unknown metabolite features. The three most stable metabolites were N6,N6-dimethyllysine (ICC = 0.82), dimethylguanidino valerate (ICC = 0.72), and N-acetylornithine (ICC = 0.72). The three least stable metabolites were palmitoylethanolamide (ICC = 0.05), ectoine (ICC = 0.09), and trimethylamine-N-oxide (ICC = 0.16). Results in the secondary dataset were similar (Spearman correlation = 0.87) to corresponding results in the primary dataset. Within-person stability over 10 years is reasonable for lipid, lipid-related, and polar metabolites, and varies by metabolite class. Additional studies are required to estimate within-person stability over 10 years of other metabolites groups.

This paper describes the design and characterization of an open-source "universal wireless electrochemical detector" (UWED). This detector interfaces with a smartphone (or a tablet) using "Bluetooth Low Energy" protocol; the smartphone provides (i) a user interface for receiving the experimental parameters from the user and visualizing the result in real time, and (ii) a proxy for storing, processing, and transmitting the data and experimental protocols. This approach simplifies the design, and decreases both the size and the cost of the hardware; it also makes the UWED adaptable to different types of analyses by simple modification of the software. The UWED can perform the most common electroanalytical techniques of potentiometry, chronoamperometry, cyclic voltammetry, and square wave voltammetry, with results closely comparable to benchtop commercial potentiostats. Although the operating ranges of electrical current and voltage of the UWED (±1.5 V, ±180 μA) are more limited than most benchtop commercial potentiostats, its functional range is sufficient for most electrochemical analyses in aqueous solutions. Because the UWED is simple, small in size, assembled from inexpensive components, and completely wireless, it offers new opportunities for the development of affordable diagnostics, sensors, and wearable devices.