Publications

Importance The current Dietary Guidelines for Americans recommend multiple healthy eating patterns. However, few studies have examined the associations of adherence to different dietary patterns with long-term risk of total and cause-specific mortality. Objective To examine the associations of dietary scores for 4 healthy eating patterns with risk of total and cause-specific mortality. Design, Setting, and Participants This prospective cohort study included initially healthy women from the Nurses’ Health Study (NHS; 1984-2020) and men from the Health Professionals Follow-up Study (HPFS; 1986-2020). Exposures Healthy Eating Index 2015 (HEI-2015), Alternate Mediterranean Diet (AMED) score, Healthful Plant-based Diet Index (HPDI), and Alternate Healthy Eating Index (AHEI). Main Outcomes and Measures The main outcomes were total and cause-specific mortality overall and stratified by race and ethnicity and other potential risk factors. Results The final study sample included 75 230 women from the NHS (mean [SD] baseline age, 50.2 [7.2] years) and 44 085 men from the HPFS (mean [SD] baseline age, 53.3 [9.6] years). During a total of 3 559 056 person-years of follow-up, 31 263 women and 22 900 men died. When comparing the highest with the lowest quintiles, the pooled multivariable-adjusted HRs of total mortality were 0.81 (95% CI, 0.79-0.84) for HEI-2015, 0.82 (95% CI, 0.79-0.84) for AMED score, 0.86 (95% CI, 0.83-0.89) for HPDI, and 0.80 (95% CI, 0.77-0.82) for AHEI ( P < .001 for trend for all). All dietary scores were significantly inversely associated with death from cardiovascular disease, cancer, and respiratory disease. The AMED score and AHEI were inversely associated with mortality from neurodegenerative disease. The inverse associations between these scores and risk of mortality were consistent in different racial and ethnic groups, including Hispanic, non-Hispanic Black, and non-Hispanic White individuals. Conclusions and Relevance In this cohort study of 2 large prospective cohorts with up to 36 years of follow-up, greater adherence to various healthy eating patterns was consistently associated with lower risk of total and cause-specific mortality. These findings support the recommendations of Dietary Guidelines for Americans that multiple healthy eating patterns can be adapted to individual food traditions and preferences.

We report the growth and characterization of core/multishell nanowire radial heterostructures, and their implementation as efficient and synthetically tunable multicolor nanophotonic sources. Core/multishell nanowires were prepared by metal-organic chemical vapor deposition with an n-GaN core and InxGa1-xN/GaN/p-AlGaN/p-GaN shells, where variation of indium mole fraction is used to tune emission wavelength. Cross-sectional transmission electron microscopy studies reveal that the core/multishell nanowires are dislocation-free single crystals with a triangular morphology. Energy-dispersive X-ray spectroscopy clearly shows shells with distinct chemical compositions, and quantitatively confirms that the thickness and composition of individual shells can be well controlled during synthesis. Electrical measurements show that the p-AlGaN/p-GaN shell structure yields reproducible hole conduction, and electroluminescence measurements demonstrate that in forward bias the core/multishell nanowires function as light-emitting diodes, with tunable emission from 365 to 600 nm and high quantum efficiencies. The ability to synthesize rationally III-nitride core/multishell nanowire heterostructures opens up significant potential for integrated nanoscale photonic systems, including multicolor lasers.

Studies of leukocyte telomere length (LTL) and adiposity have produced conflicting results, and the relationship between body mass index (BMI) and telomere length throughout life remains unclear. We therefore tested association of adult LTL measured in 5,598 participants with: i) childhood growth measures (BMI and age at adiposity rebound (AR)); ii) change in BMI from childhood to adulthood and iii) adult BMI, waist-to-hip ratio (WHR), body adiposity index (BAI). Childhood BMI at AR was positively associated with LTL at 31 years in women (P = 0.041). Adult BMI and WHR in both men (P = 0.025 and P = 0.049, respectively) and women (P = 0.029 and P = 0.008, respectively), and BAI in women (P = 0.021) were inversely associated with LTL at 31 years. An increase in standardised BMI between early childhood and adulthood was associated with shorter adult LTL in women (P = 0.008). We show that LTL is inversely associated with multiple measures of adiposity in both men and women. Additionally, BMI increase in women from childhood to adulthood is associated with shorter telomeres at age 31, potentially indicating accelerated biological ageing.

Background: Plant-based diets have been associated with a lower risk of type 2 diabetes. However, the underlying mechanisms are not completely understood, and the evidence using objective approaches to assess the adherence of plant-based diets is limited. Methods: In the Nurses’ Health Study (NHS), NHSII, and Health Professionals Follow-Up Study, we characterized the plasma metabolome related to plant-based diets and examined its association with the incidence of type 2 diabetes among 10 699 participants. Plasma metabolomic profiling was conducted by liquid chromatography-tandem mass spectrometry. Adherence to plant-based diets was assessed by three plant-based diet indices derived from the food frequency questionnaire: an overall plant-based diet index (PDI), a healthful PDI (hPDI), and an unhealthful PDI (uPDI). Metabolomic signatures reflecting the adherence to plant-based diets were created using elastic net regression, and their associations with risk of type 2 diabetes were subsequently evaluated using multivariable Cox proportional hazards regression. Results: Among 263 metabolites measured, nearly half were significantly associated with PDI (41.4%, 109 of 263), hPDI (51.7%, 136 of 263), and uPDI (40.3%, 106 of 263) after Bonferroni correction. We developed a metabolomic signature comprising 53 metabolites for PDI, 76 metabolites for hPDI, and 88 metabolites for uPDI, each robustly correlated with the corresponding diet index (r=0.34-0.36 for PDI, 0.43-0.44 for hPDI, and 0.36-0.37 for uPDI). We observed an inverse association of PDI metabolomic signature (HR 0.86, 95% CI 0.79-0.93 per one standard deviation) and hPDI metabolomic signature (0.79, 0.72-0.86) with type 2 diabetes risk after adjustment for body mass index and other potential confounders. These two inverse associations remained significant even further adjusting for the corresponding diet index PDI and hPDI. The metabolomic signature for uPDI was not associated with type 2 diabetes risk (1.00, 0.93-1.09). Conclusion: Plasma metabolome can robustly reflect adherence and metabolic response to plant-based diets. Metabolomic signatures reflecting greater adherence to an overall plant-based diet, especially a healthful plant-based diet, were associated with a lower risk of type 2 diabetes. These findings support and provide mechanistic insights on the important role of healthful plant-based diets in diabetes prevention.

Transistor-based nanoelectronic sensors are capable of label-free real-time chemical and biological detection with high sensitivity and spatial resolution, although the short Debye screening length in high ionic strength solutions has made difficult applications relevant to physiological conditions. Here, we describe a new and general strategy to overcome this challenge for field-effect transistor (FET) sensors that involves incorporating a porous and biomolecule permeable polymer layer on the FET sensor. This polymer layer increases the effective screening length in the region immediately adjacent to the device surface and thereby enables detection of biomolecules in high ionic strength solutions in real-time. Studies of silicon nanowire field-effect transistors with additional polyethylene glycol (PEG) modification show that prostate specific antigen (PSA) can be readily detected in solutions with phosphate buffer (PB) concentrations as high as 150 mM, while similar devices without PEG modification only exhibit detectable signals for concentrations ≤10 mM. Concentration-dependent measurements exhibited real-time detection of PSA with a sensitivity of at least 10 nM in 100 mM PB with linear response up to the highest (1000 nM) PSA concentrations tested. The current work represents an important step toward general application of transistor-based nanoelectronic detectors for biochemical sensing in physiological environments and is expected to open up exciting opportunities for in vitro and in vivo biological sensing relevant to basic biology research through medicine.

Decline in both telomere length and physical fitness over the life course may contribute to increased risk of several chronic diseases. The relationship between telomere length and aerobic and muscular fitness is not well characterized. We examined whether there are cross-sectional associations of mean relative leukocyte telomere length (LTL) with objective measures of aerobic fitness, muscle strength, and muscle endurance, using data on 31-year-old participants of the Northern Finland Birth Cohort 1966 (n = 4,952-5,205, varying by exposure-outcome analysis). Aerobic fitness was assessed by means of heart rate measurement following a standardized submaximal step test; muscular fitness was assessed by means of a maximal isometric handgrip strength test and a test of lower-back trunk muscle endurance. Longer LTL was associated with higher aerobic fitness and better trunk muscle endurance in models including adjustment for age, sex, body mass index, socioeconomic position, diet, smoking, alcohol consumption, physical activity level, and C-reactive protein. In a sex-stratified analysis, LTL was not associated with handgrip strength in either men or women. LTL may relate to aspects of physical fitness in young adulthood, but replication of these findings is required, along with further studies to help assess directions and causality in these associations.

The genome-wide association study (GWAS) approach has discovered hundreds of genetic variants associated with diseases and quantitative traits. However, despite clinical overlap and statistical correlation between many phenotypes, GWAS are generally performed one-phenotype-at-a-time. Here we compare the performance of modelling multiple phenotypes jointly with that of the standard univariate approach. We introduce a new method and software, MultiPhen, that models multiple phenotypes simultaneously in a fast and interpretable way. By performing ordinal regression, MultiPhen tests the linear combination of phenotypes most associated with the genotypes at each SNP, and thus potentially captures effects hidden to single phenotype GWAS. We demonstrate via simulation that this approach provides a dramatic increase in power in many scenarios. There is a boost in power for variants that affect multiple phenotypes and for those that affect only one phenotype. While other multivariate methods have similar power gains, we describe several benefits of MultiPhen over these. In particular, we demonstrate that other multivariate methods that assume the genotypes are normally distributed, such as canonical correlation analysis (CCA) and MANOVA, can have highly inflated type-1 error rates when testing case-control or non-normal continuous phenotypes, while MultiPhen produces no such inflation. To test the performance of MultiPhen on real data we applied it to lipid traits in the Northern Finland Birth Cohort 1966 (NFBC1966). In these data MultiPhen discovers 21% more independent SNPs with known associations than the standard univariate GWAS approach, while applying MultiPhen in addition to the standard approach provides 37% increased discovery. The most associated linear combinations of the lipids estimated by MultiPhen at the leading SNPs accurately reflect the Friedewald Formula, suggesting that MultiPhen could be used to refine the definition of existing phenotypes or uncover novel heritable phenotypes.

Background: Along with the shift in consumption patterns of carbohydrate staple foods in Indonesia, many communities are abandoning local traditional foods such as tubers and sago and turning to white rice. Objective: Considering the rise of modern living patterns that are loved by teenagers and young adults, the researchers aimed to identify the basic food consumption patterns of adolescents and young people in Indonesia and the factors that influence them. Methods: The subjects involved in this study were 108 Universitas Gadjah Mada students representing various regions and tribes in Indonesia. The proportion of each part of Indonesia was determined by the proportionate stratified random sampling technique, while the research subjects were selected by purposive sampling. Subjects were interviewed using the semi-quantitative food frequency questionnaire (SQ-FFQ). Data on knowledge factors related to nutrition and perceptions were obtained using a separate questionnaire. Results: The most consumed staple carbohydrate foods are cereals, especially white rice (82%), tubers (10.6%), noodles, pasta and bread (12.3%) and sago (1.8%). Several factors that influence the consumption pattern significantly (p<0.05) are sex, place of origin, and nutritional status. Conclusions: There is a high dependency on white rice among young adults in Yogyakarta, Indonesia. The culture and place of origin have an important role in shaping the pattern of carbohydrate consumption. Strategic interventions are needed to increase youth food diversification.

The structural and mechanical properties of single-walled carbon nanotubes (SWNTs) make them ideal tips for scanning probe microscopies such as atomic force microscopy (AFM). However, the ideal nanotube probe, which corresponds to an individual SWNT, has been difficult to produce in high yield. To overcome this difficulty, a straightforward and easily implemented method that enables very high-yield fabrication of individual SWNT probes has been developed. This new method is based upon the observation that microfabricated tips can "pick up" vertically aligned SWNTs grown from planar substrate surfaces. Substrates with isolated, vertically aligned SWNT are first prepared by chemical vapor deposition and then imaged with commercial microfabricated silicon AFM tips. The silicon tips pick up individual SWNTs from the substrate during imaging to create well-aligned SWNT probes. The SWNT tips have been etched using a procedure that allows variation of the nanotube length with 2 nm control. Studies of gold nanocluster standards demonstrate that these individual SWNT tips are capable of high resolution and robust imaging in air and fluids, and thus these tips are expected to open up new opportunities in nanoscale science and technology.

'Physicochemical Properties of Nanoparticles in Relation with Toxicity' published in 'Encyclopedia of Nanotechnology'

'Physical-Chemical Etching' published in 'Encyclopedia of Nanotechnology'

This paper describes a procedure for rapidly and conveniently prototyping microfluidic devices that are useful with aqueous solutions. A design (with diameters of channels 20 µm) is created in a computer-aided design program and printed at high resolution on a transparency. This transparency is used as a mask in photolithography to create a master in positive relief photoresist: casting poly(dimethyl siloxane) (PDMS) against this master yields a polymeric replica containing a network of bas-relief channels. The channels are closed and sealed irreversibly by oxidizing the replica and another flat substrate (PDMS, glass, silicon, silicon oxide) in an oxygen plasma and bringing the two surfaces into conformal contact. Oxidation of the polymer allows the formation of a seal without using adhesives; it also generates channels that support electro-osmotic flow (EOF) and fill easily with aqueous solutions. Two microfluidic devices - a fluidic switch and a side channel flow controller - have been fabricated using this rapid prototyping methodology. These devices were tested using aqueous solutions as the test fluid and actuated by EOF.

Introduction: As sodium intake (Na) rises, so does blood pressure. However, the results of cohort studies that relate Na to cardiovascular disease (CVD) are inconsistent. We systematically reviewed the quality of cohort studies for methodological issues that could bias assessments of the relationship between Na and CVD. Hypothesis: Methodological limitations are common in cohort studies assessing the link between Na and CVD. Methods: We included all known articles that examined the association between Na and CVD or all-cause mortality, coronary heart disease, stroke or heart failure. We divided articles based on 1) type of study population, i.e. general population versus targeted samples at elevated risk of CVD and 2) method of Na assessment. We looked for the presence of random and systematic error in Na assessment, analytic issues such as under-adjustment, and potential for residual confounding and reverse causality. Results: We identified 26 studies with 31 independent samples. Of the samples, 13 found at least one direct association between Na and CVD, 10 at least one inverse or J-shaped association, and eight only null associations. 20 were from the general population and 11 from targeted groups. Urine collection was used to assess Na in 13 (24-hour collections in 11) and diet-based measures in 18. Overall, 81% of the 31 samples had a high potential for random errors in sodium assessment, eight of the 17 with sufficient information had systematic errors in Na assessment, 29% were conducted in targeted groups with high potential for reverse causality, and 52% were inadequately adjusted. Conclusions: Methodological issues are common in observational studies linking Na and CVD.