Publications

Almost all pneumatic and hydraulic actuators useful for mesoscale functions rely on hard valves for control. This article describes a soft, elastomeric valve that contains a bistable membrane, which acts as a mechanical "switch" to control air flow. A structural instability-often called "snap-through"-enables rapid transition between two stable states of the membrane. The snap-upward pressure, ΔP1 (kilopascals), of the membrane differs from the snap-downward pressure, ΔP2 (kilopascals). The values ΔP1 and ΔP2 can be designed by changing the geometry and the material of the membrane. The valve does not require power to remain in either "open" or "closed" states (although switching does require energy), can be designed to be bistable, and can remain in either state without further applied pressure. When integrated in a feedback pneumatic circuit, the valve functions as a pneumatic oscillator (between the pressures ΔP1 and ΔP2), generating periodic motion using air from a single source of constant pressure. The valve, as a component of pneumatic circuits, enables (i) a gripper to grasp a ball autonomously and (ii) autonomous earthworm-like locomotion using an air source of constant pressure. These valves are fabricated using straightforward molding and offer a way of integrating simple control and logic functions directly into soft actuators and robots.

Multiwalled carbon nanotube (MWNT) probe microscopy tips have been functionalized with gases, activated in a transient arc produced at the tip ends. Adhesion measurements between these tips and hydroxyl-terminated monolayers versus pH reveal that MWNT tips reacted in O2, H2 and N2 display acidic, pH-independent and basic properties, respectively. MWNT tips derivatized in O2/N2 and H2/N2 mixtures demonstrate the greater reactivity of carbon nanotubes towards O2 and H2, respectively. Moreover, the chemical reactivity of tips functionalized in N2 suggests termination in aromatic nitrogen heterocycles. Tip-activated gas functionalization of MWNTs provides facile generation of chemically sensitive nanoprobes.

A principal challenge in wound healing is a lack of cell recruitment, cell infiltration, and vascularization, which occurs in the absence of temporal and spatial cues. We hypothesized that a scaffold that expands due to local changes in pH may alter oxygen and nutrient transport and the local cell density, leading to enhanced cell deposition and survival. In this study, we present a pH-responsive scaffold that increases oxygen transport, as confirmed by our finite element model analysis, and cell proliferation relative to a non-responsive scaffold. In vivo, responsive scaffolds induce a pro-healing gene expression profile indicative of enhanced angiogenesis, granulation tissue formation, and tissue remodeling. Scaffolds that stretch in response to their environment may be a hallmark for tissue regeneration.

<p> </p> <p><strong>Objective</strong></p> <p>We evaluated prospectively the association between incident early- (diagnosed under the age of 40 years) and later-onset type 2 diabetes, and early- (diagnosed before age 50) and later-onset cancer risk.</p> <p><strong>Research Design and Methods</strong></p> <p>We prospectively followed 228,073 eligible participants in the Nurses’ Health Studies for up to 38 years. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox models.</p> <p><strong>Results</strong></p> <p>We documented 18,290 type 2 diabetes, 6,520 early-onset cancer, and 36,907 later-onset cancer cases during follow-up. In fully-adjusted analyses, early-onset type 2 diabetes was associated with increased risk of early-onset total cancer (HR, 95%CI was 1.47, 1.06-2.04), diabetes-related cancer (2.11, 1.38-3.23), and obesity-related cancer (1.75, 1.08-2.82), and the risk elevations were restricted to those with BMI at age 18 of ≥21 kg/m2 (total cancer: 1.75, 1.20-2.56; diabetes-related cancer: 2.43, 1.50-3.94; obesity-related cancer: 1.84, 1.05-3.22). Early-onset type 2 diabetes was associated with higher risk of later-onset diabetes-related and obesity-related cancer specifically among individuals with higher BMI at age 18. Later-onset type 2 diabetes was associated with higher risk of later-onset total cancer (1.15, 1.11-1.20), diabetes-related cancer (1.17, 1.12-1.22), and obesity-related cancer (1.18, 1.13-1.24). In analyses based on refined timing, the HRs attenuated substantially with aging.</p> <p><strong>Conclusions</strong></p> <p>Incident early-onset type 2 diabetes was associated with increased risk of early-onset total cancer, and diabetes- and obesity-related cancer, especially in those with higher BMI at age 18. The impact of early-onset type 2 diabetes on cancer risk may be inherently stronger than that of later-onset type 2 diabetes.</p>

OBJECTIVE—The purpose of this study was to evaluate the associations of BMI versus metabolic syndrome with cardiovascular diseases (CVDs) in elderly Chinese individuals. RESEACH DESIGN AND METHODS—We conducted a population-based cross-sectional study in an urban sample of 2,334 elderly subjects (943 men and 1,391 women). Subjects were classified by BMI (≤18.5, <24, <28, and ≥28 kg/m2) and the presence or absence of metabolic syndrome, which was defined by International Diabetes Federation (IDF) criteria. CVDs included clinically diagnosed coronary heart disease (CHD), stroke, and peripheral arterial disease (PAD). RESULTS—The prevalence rates of overweight (BMI ≥25 kg/m2) and metabolic syndrome according to the IDF criteria were 56.3% (53.9% in men and 57.9% in women) and 46.3% (34.8% in men and 54.1% in women), respectively. Increasing BMI was strongly associated with a higher risk of CHD, stroke, and PAD even after adjustments for metabolic syndrome and other CVD risk factors. Stratified analysis of participants with or without metabolic syndrome showed that BMI was independently associated with CHD, stroke, and PAD. CONCLUSIONS—Both overweight and metabolic syndrome are highly prevalent in this elderly Chinese population. BMI, as a measure of overall adiposity, is strongly associated with increased prevalence of CVD independent of metabolic syndrome.

OBJECTIVE Compelling biological pathways suggest that selenium (Se) may lower onset of type 2 diabetes mellitus (T2DM), but very few studies have evaluated this relationship, with mixed results. We examined the association between toenail Se and incidence of T2DM. RESEARCH DESIGN AND METHODS We performed prospective analyses in two separate U.S. cohorts, including 3,630 women and 3,535 men, who were free of prevalent T2DM and heart disease at baseline in 1982–1983 and 1986–1987, respectively. Toenail Se concentration was quantified using neutron activation analysis, and diabetes cases were identified by biennial questionnaires and confirmed by a detailed supplementary questionnaire. Hazard ratios of incident T2DM according to Se levels were calculated using Cox proportional hazards. RESULTS During 142,550 person-years of follow-up through 2008, 780 cases of incident T2DM occurred. After multivariable adjustment, the risk of T2DM was lower across increasing quintiles of Se, with pooled relative risks across the two cohorts of 1.0 (reference), 0.91 (95% CI 0.73–1.14), 0.78 (0.62–0.99), 0.72 (0.57–0.91), and 0.76 (0.60–0.97), respectively (P for trend = 0.01). Results were similar excluding the few individuals (4%) who used Se supplements. In semiparametric analyses, the inverse relationship between Se levels and T2DM risk appeared to be linear. CONCLUSIONS At dietary levels of intake, individuals with higher toenail Se levels are at lower risk for T2DM. Further research is required to determine whether varying results in this study versus prior trials relate to differences in dose, source, statistical power, residual confounding factors, or underlying population risk.

A large number of studies have shown that physical activity improves overall health, reduces the risks of many chronic diseases, and may prevent premature death. It is unclear whether the benefits of physical activity found at midlife also occur in physically active individuals 65 and older. This study used data from the Nurses' Health Study to examine the relation between midlife physical activity, including walking and successful aging defined as a full spectrum of health outcomes. The study population was comprised of 13,535 women enrolled in the Nurses' Health Study, who were free of major chronic diseases at baseline in 1986 and had survived to age 70 years or older as of 1995 to 2001. The concept of successful aging accounts for both comorbidities and disabilities, and was used to evaluate the overall health status of the study participants. Successful aging was defined as no history of 10 major chronic diseases and coronary artery bypass graft surgery, no physical disabilities, and no impairment in cognitive function or mental health limitations. A successful survivor was any participant who met these criteria and survived to at least age 70 years. Metabolic-equivalent tasks (METs) measured in hours per week were used to calculate energy expenditure. The study participants were grouped into quintiles of total METs. Adjustment for covariables was performed with multivariate logistic regression models. A total of 1456 (10.8%) of the 13,535 participants were successful survivors. The adjusted odds ratios (aORs) of successful survival associated with each quintile were estimated, with the lowest quintile defined as the reference. Multivariate analysis showed that higher physical activity levels at midlife, as measured by METs, were significantly associated with greater likelihood of successful survival. Significant increases in the odds of successful survival were found; the aORs across quintiles (with 95% confidence intervals) were 1 (reference), 0.98 (0.80–1.20), 1.37 (1.13–1.65), 1.34 (1.11–1.61), and 1.99 (1.66–2.38); P < 0.001 for trend. A significant elevation in the odds of successful survival was also associated with increasing energy expenditure from walking; the aORs (95% confidence intervals) across quintiles of walking were 1 (reference), 0.99 (0.80–1.21), 1.19 (0.97–1.45), 1.50 (1.24–1.82), and 1.47 (1.22–1.79); P < 0.001 for trend. These findings present evidence that midlife physical activity is associated with increased odds of exceptional health status among women who are initially healthy at midlife and survive to older ages. The data suggest that physical activity can promote successful survival beyond just extending the lifespan.

Background Metabolomics is a promising tool of cardiovascular biomarker discovery. We systematically reviewed the literature on comprehensive metabolomic profiling in association with incident cardiovascular disease ( CVD ). Methods and Results We searched MEDLINE and EMBASE from inception to January 2016. Studies were eligible if they pertained to adult humans; followed an agnostic and/or comprehensive approach; used serum or plasma (not urine or other biospecimens); conducted metabolite profiling at baseline in the context of examining prospective disease; and included myocardial infarction, stroke, and/or CVD death in the CVD outcome definition. We identified 12 original articles (9 cohort and 3 nested case‐control studies); participant numbers ranged from 67 to 7256. Mass spectrometry was the predominant analytical method. The number and chemical diversity of metabolites were very heterogeneous, ranging from 31 to &gt;10 000 features. Four studies used untargeted profiling. Different types of metabolites were associated with CVD risk: acylcarnitines, dicarboxylacylcarnitines, and several amino acids and lipid classes. Only tiny improvements in CVD prediction beyond traditional risk factors were observed using these metabolites (C index improvement ranged from 0.006 to 0.05). Conclusions There are a limited number of longitudinal studies assessing associations between comprehensive metabolomic profiles and CVD risk. Quantitatively synthesizing the literature is challenging because of the widely varying analytical tools and the diversity of methodological and statistical approaches. Although some results are promising, more research is needed, notably standardization of metabolomic techniques and statistical approaches. Replication and combinations of novel and holistic methodological approaches would move the field toward the realization of its promise.

Women with polycystic ovary syndrome (PCOS) suffer from anovulatory infertility and hospital-based studies suggest that they have an increased risk of spontaneous abortion. Our aim was to investigate the proportion of women, with self-reported oligo-amenorrhea and/or hirsutism in a general population, who had suffered from infertility, the percentage of them managing to conceive and their rate of spontaneous abortion.At age 31, a postal questionnaire including questions about hirsutism and oligo-amenorrhea was sent to all women from the population-based Northern Finland Birth Cohort 1966 (total n = 5889). Of these, 4535 (79.5%) answered the questionnaire, 1103 reported hirsutism and/or oligo/amenorrhea (symptomatic women) and 3420 were non-symptomatic. The fecundability ratio (FR) was defined as the probability of conception of a clinically detectable pregnancy within 12 months.The overall pregnancy (77.7% versus 75.6%) and spontaneous abortion (19.3% versus 18.6%) rates did not differ between the two groups and the risk of spontaneous abortion was not associated with body mass index (BMI), waist-to-hip ratio (WHR) or waist circumference. Symptomatic women had suffered more often from infertility than non-symptomatic women (19.4% versus 11.1%, P < 0.01). Oligo-amenorrhea and/or hirsutism (FR = 0.74, P < 0.001) and obesity (FR = 0.68, P = 0.002) were both independently associated with decreased fecundability, but symptomatic women had become pregnant and had one or two successful deliveries as often as non-symptomatic women.Women with self-reported oligo-amenorrhea and/or hirsutism had lower fecundability and suffered more often from infertility, but had at least one delivery as often as non-symptomatic women, and did not exhibit an increased risk of spontaneous abortion.