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Higher baseline urinary neutrophil gelatinase-associated lipocalin was associated with worse cognitive scores at baseline. Lower concentrations of baseline serum bicarbonate (higher is better) were associated with lower cognitive scores at baseline. We found no associations with urine markers with longitudinal changes in cognition.

INTRODUCTION Lowering blood pressure (BP) reduces the risk for cognitive impairment and the progression of cerebral white matter lesions. It is unclear whether hypertension control also influences plasma biomarkers related to Alzheimer's disease and non-disease-specific neurodegeneration. METHODS We examined the effect of intensive (

Purpose The association between CVD risk factors and mortality is well established, however, current tools for addressing subgroups have focused on the overall burden of disease. The identification of risky combinations of characteristics may lead to a better understanding of physiologic pathways that underlie morbidity and mortality in older adults. Methods Participants included 5067 older adults from the Cardiovascular Health Study, followed for up to 6 years. Using latent class analysis (LCA), we created CV damage phenotypes based on probabilities of abnormal brain infarctions, major echocardiogram abnormalities, N-terminal probrain natriuretic peptide, troponin T, interleukin-6, c reactive-protein, galectin-3, cystatin C. We assigned class descriptions based on the probability of having an abnormality among risk factors, such that a healthy phenotype would have low probabilities in all risk factors. Participants were assigned to phenotypes based on the maximum probability of membership. We used Cox-proportional hazards regression to evaluate the association between the categorical CV damage phenotype and all-cause and CVD-mortality. Results The analysis yielded 5 CV damage phenotypes consistent with the following descriptions: healthy (59%), cardio-renal (11%), cardiac (15%), multisystem morbidity (6%), and inflammatory (9%). All four phenotypes were statistically associated with a greater risk of all-cause mortality when compared with the healthy phenotype. The multisystem morbidity phenotype had the greatest risk of all-cause death (HR: 4.02; 95% CI: 3.44, 4.70), and CVD-mortality (HR: 4.90, 95% CI: 3.95, 6.06). Conclusions Five CV damage phenotypes emerged from CVD risk factor measures. CV damage across multiple systems confers a greater mortality risk compared to damage in any single domain.

Covert brain infarcts and white matter hyperintensities (WMHs), incidental markers of brain microvascular disease commonly seen on brain MRIs in older adults, have been associated with falls and lower bone mineral density. We found covert infarcts and WMHs may also be associated with an increased risk of future hip fracture.To determine whether covert infarcts and white matter hyperintensities (WMHs) are associated with increased risk of incident hip fracture.A prospective cohort of 3373 community-dwelling adults aged ≥ 65 years enrolled in the Cardiovascular Health Study with a brain MRI (1992-1993) was analyzed. Covert infarcts were categorized by number of infarcts and largest infarct size. WMH burden was assessed by radiologists and graded qualitatively from 0 (no WMHs) to 9 (extensive).Participants had 465 incident hip fractures during a mean follow-up of 12.8 years. The demographic-adjusted hazard of incident hip fracture was 32% higher among participants with ≥ 1 covert infarct compared to those without infarcts (hazard ratio (HR) 1.32; 95% CI, 1.08-1.62). The hazard of incident hip fracture was similar after further adjustment for medications and medical history (HR = 1.34; 95% CI, 1.08-1.65), but attenuated following additional adjustment for functional status, frailty, and falls (HR = 1.25; 95% CI, 0.99-1.57). Fully adjusted hazard of incident hip fracture per increase in infarct number was 1.10 (95% CI, 0.98-1.23); risk in individuals whose largest infarct was ≥ 20 mm versus 3 to 20 mm was similar. Compared with WMH grades 0-1, the demographic-adjusted hazard of hip fracture was 1.34 (95% CI, 1.09-1.66) and 1.83 (95% CI, 1.37-2.46), respectively, for WMH grades 2-3 and 4-9. The hazard was similar following adjustment for medications and medical history (grades 2-3: HR = 1.32; 95% CI, 1.05-1.64; grades 4-9: HR = 1.69; 95% CI, 1.23-2.30), but attenuated following additional adjustment for functional status, frailty, and falls (grades 2-3: HR = 1.24; 95% CI, 0.98-1.56; grades 4-9: HR = 1.34; 95% CI, 0.95-1.90).Older, community-dwelling adults with covert infarcts or WMHs may be at increased risk of hip fracture.

Urine biomarker concentrations reflecting kidney tubule injury and dysfunction were not associated with brain MRI measures. Higher eGFR was associated with lower total brain cerebral blood flow. This is the first evaluation of the relationship of kidney tubule biomarkers with brain imaging by MRI in patients with CKD.

Elevated serum phosphate and parathyroid hormone (PTH) concentrations are associated with cardiovascular events, bone disease, and mortality in patients on maintenance hemodialysis. Although circadian changes are known in people with CKD, it is unknown whether differences occur in these parameters over the course of a day in people receiving hemodialysis.We used clinical data from Fresenius Medical Care US dialysis clinics to determine how the time of day when measurements were collected (hemodialysis treatment start time) may be associated with serum phosphate and PTH concentrations. We used harmonic regression to assess these associations while accounting for demographic data and treatment parameters.A total of 96,319 patients receiving maintenance hemodialysis were included in this analysis. Patients had a mean age of 64±14 years, 43% were women, and dialysis start times ranged from 3:00 am to 7:59 pm. The mean serum phosphate concentration was 5.2±1.5 mg/dl, and the median PTH was 351 pg/ml (interquartile range [IQR], 214-547). In fully adjusted models, serum phosphate had a nadir at 11:00 am of 4.97 (IQR, 4.94-5.01) mg/dl and a peak at 7:00 pm of 5.56 (IQR, 5.50-5.62) mg/dl. Serum PTH had a nadir at 9:00 am of 385 (IQR, 375-395) pg/ml and a peak at 7:00 pm of 530 (IQR, 516-547) pg/ml.Among patients receiving maintenance hemodialysis, concentrations of PTH and phosphate before a dialysis session vary with the time of day that these values are measured. Consideration of whether these values were obtained at peak or nadir times of the day may be important in treatment decisions.

Recent studies have suggested that 25-hydroxyvitamin D (25(OH)D) may be a poor biomarker of bone health, in part because measured levels incorporate both protein-bound and free vitamin D. The ratio of its catabolic product (24,25-dihydroxyvitamin D [24,25(OH)2 D]) to 25(OH)D (the vitamin D metabolite ratio [VMR]) may provide more information on sufficient vitamin D stores and is not influenced by vitamin D-binding protein concentrations. We evaluated whether the VMR or 25(OH)D are more strongly associated with bone loss and fracture risk in older adults. We performed a retrospective cohort study of 786 community-dwelling adults aged 70 to 79 years who participated in the Health Aging and Body Composition study. Our primary outcomes were annual changes in bone density and incident fracture. The mean age of these participants was 75 ± 3 years, 49% were female, 42% were Black, and 23% had an estimated glomerular filtration rate (eGFR)

Nearly one-third of individuals in the U.S. will be diagnosed with an anxiety disorder during their lifetime. Receiving that label can evoke self-stigma, with self-stigma relating to greater symptom severity and negatively impacting treatment outcomes. A lesser-studied variable related to self-stigma is etiological attributions about symptoms, including biological and psychological attributions. The current study examined interrelations among self-stigma, etiological attributions, and symptom severity among 213 individuals diagnosed with an anxiety disorder who completed a cognitive-behavioral treatment (CBT) program. How self-stigma and etiological attributions related to symptom improvement following the program was examined in a subset of participants. Etiological attributions and self-stigma shared positive associations with symptom severity. Regression analyses indicated that, when controlling for overlap among self-stigma and etiological attributions, psychological attributions emerged as particularly relevant for understanding symptom severity. Changes in self-stigma and attributions were positively associated with changes in symptom severity following the CBT program. Study implications are discussed.

RATIONALE AND OBJECTIVE: The associations of glomerular markers of kidney disease (eGFR and albuminuria) with frailty and cognition are well established. However, the relationship of kidney tubular injury and dysfunction with frailty and cognition are unknown. STUDY DESIGN: Observational cross-sectional study. SETTING & PARTICIPANTS: 2,253 participants with eGFR < 60 ml/min/1.73m(2) in the Systolic Blood Pressure Intervention Trial EXPOSURES: Eight urine biomarkers: Interleukin-18 [IL-18, pg/mL], kidney injury molecule-1 [KIM-1, pg/mL], neutrophil gelatinase-associated lipocalin [NGAL, ng/mL], chitinase-3-like protein-1 [YKL-40, pg/mL], monocyte chemoattractant protein-1 [MCP-1, pg/mL], α−1 microglobulin [α1M mg/g], beta-2 microglobulin [β2M ng/mL], and uromodulin [Umod ng/mL]. OUTCOMES: Frailty was measured using a previously validated frailty index (FI), categorized as fit (FI ≤ 0.10), less fit (0.10 < FI ≤ 0.21) and frail (FI > 0.21). Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA). ANALYTICAL APPROACH: Associations between kidney tubule biomarkers with categorical FI were evaluated using multinomial logistic regression with the fit group as the reference. Cognitive function was evaluated using linear regression. Models were adjusted for demographic, behavioral and clinical variables including eGFR and urine albumin. RESULTS: Three of the 8 urine biomarkers of tubule injury and dysfunction were independently associated with FI. Each two-fold higher level of urine KIM-1, a marker of tubule injury, was associated with a 1.22 [95% CI: 1.01, 1.49) fold greater odds of being in frail group. MCP-1, a marker of tubulo-interstitial fibrosis, was associated with a 1.30 [95% CI 1.04, 1.64] greater odds of being in frail group, and α1M, a marker of tubule re-absorptive capacity, was associated with a 1.48 [95% CI 1.11, 1.96] greater odds. These associations were independent of confounders including eGFR and urine albumin, and were stronger than those of urine albumin with frailty index (1.15 [95% CI 0.99, 1.34]). Higher urine β2M, another marker of tubule reabsorptive capacity, was associated with worse cognitive scores at baseline (β: ‒0.09; 95% CI ‒0.17, ‒0.01). Urine albumin was not associated with cognitive function. LIMITATIONS: Cross-sectional design, FI may not be generalizable in other populations. CONCLUSIONS: Urine biomarkers of tubule injury, fibrosis and proximal tubule reabsorptive capacity are variably associated with FI and worse cognition, independent of glomerular markers of kidney health. Future studies are needed to validate these results among other patient populations.

Objective To examine whether self-reported functional status modified the association between blood pressure (BP) and cognitive decline among older adults. Methods The study included 2097 US adults aged 75 years and older from the Cardiovascular Health Study, followed for up to 6 years. Functional status was ascertained by self-reported limitation in activities of daily living (ADL; none vs. any). Cognitive function was assessed by the Modified Mini Mental State Exam (3MSE). We used linear mixed models to examine whether the presence of at least one ADL limitation modified the association between BP and cognitive decline. Potential confounders included demographics, physiologic measures, antihypertensive medication use and apolipoprotein E e4 allele. We conducted stratified analyses for significant interactions between BP and ADL. Results The association between BP and change in 3MSE differed by baseline ADL limitation. Among participants without ADL limitation, elevated systolic BP (≥140 mmHg) was associated with a 0.15 decrease (95% CI -0.24 to -0.07); P value for interaction less than 0.001, whereas in those with an ADL limitation, elevated systolic BP was independently associated with a 0.30 increase in 3MSE scores per year (95% CI 0.06-0.55). Elevated diastolic BP (≥80 mmHg) was associated with an increase in cognitive function in both groups, although the increase was greater in those with ADL limitation (0.47 points per year vs. 0.18 points per year, P value for interaction = 0.01). Conclusion Elevated BP appears to be associated with a decrease in cognitive scores among functioning older adults, and modest improvements in cognitive function among poorly functioning elders.

BACKGROUND The importance of systemic inflammation, measured by C-reactive protein, in cognitive decline has been demonstrated; however, the role of vascular inflammation is less understood. Pentraxin 3 (PTX3) is a novel marker of vascular inflammation. METHODS We followed adults 65 and older, free of cardiovascular disease (CVD) for up to 9 years (n = 1,547) in the Cardiovascular Health Study. We evaluated the relationship between PTX3 and change in cognitive function, measured using the Modified Mini-Mental State Examination (3MSE), and incident cognitive impairment (3MSE < 80). Mediation by CVD events, and effect modification by sex and apolipoprotein E ɛ4 allele (APOE4) were also examined. RESULTS The average decline in 3MSE was 0.77 points per year. The association between PTX3 and change in 3MSE differed between women and men (p = .02). In the adjusted model, each standard deviation higher in PTX3 was associated with a 0.20 greater decline in 3MSE score per year in women over follow-up (95% CI: -0. 37, -0.03; p = .02), compared to no change in men (β = 0.07; 95% CI: -0.08, 0.22). CVD events had a minor effect on the associations. No effect modification by APOE4 was found, although we observed the association of PTX3 and cognitive impairment in women was attenuated and nonsignificant after adjustment for APOE4. There was a paradoxical protective association between PTX3 and reduced cognitive impairment in men, even after adjustment for APOE4. CONCLUSIONS We found that vascular inflammation was significantly associated with cognitive decline in older women, but not men.

Background The importance of systemic inflammation, measured by C-reactive protein, in cognitive decline has been demonstrated; however, the role of vascular inflammation is less understood. Pentraxin 3 (PTX3) is a novel marker of vascular inflammation. Methods We followed adults 65 and older, free of cardiovascular disease (CVD) for up to 9 years (n = 1,547) in the Cardiovascular Health Study. We evaluated the relationship between PTX3 and change in cognitive function, measured using the Modified Mini-Mental State Examination (3MSE), and incident cognitive impairment (3MSE < 80). Mediation by CVD events, and effect modification by sex and apolipoprotein E ɛ4 allele (APOE4) were also examined. Results The average decline in 3MSE was 0.77 points per year. The association between PTX3 and change in 3MSE differed between women and men (p = .02). In the adjusted model, each standard deviation higher in PTX3 was associated with a 0.20 greater decline in 3MSE score per year in women over follow-up (95% CI: −0. 37, −0.03; p = .02), compared to no change in men (β = 0.07; 95% CI: −0.08, 0.22). CVD events had a minor effect on the associations. No effect modification by APOE4 was found, although we observed the association of PTX3 and cognitive impairment in women was attenuated and nonsignificant after adjustment for APOE4. There was a paradoxical protective association between PTX3 and reduced cognitive impairment in men, even after adjustment for APOE4. Conclusions We found that vascular inflammation was significantly associated with cognitive decline in older women, but not men.

Data routinely collected in observational studies from phone calls, medical records, and death certificates can be used to categorize dementia, though there may be misclassification. We applied probabilistic bias analyses to assess the magnitude, direction, and uncertainty of the error due to misclassification of dementia data in the Cardiovascular Health Study (CHS). We categorized dementia among all participants (73,284 person-years) using medications, ICD-9 codes, use of proxy, and death certificates, and compared to the gold standard adjudicated dementia in the CHS Memory Studies (28,250 person-years). Using the gold standard, positive (PPV) and negative predictive values (NPV) of dementia categorization were estimated within strata defined by age and sex. In probabilistic bias analyses, we reclassified participants from the full study using estimated PPVs and NPVs in 5,000 replicates. We estimated the hazard ratio (HR) of dementia associated with age, race, sex, hypertension, diabetes, and APOE4 genotype in this bias analysis and compared these results to those using original data. ICD-9 codes had low specificity and were excluded in further analyses. The NPV was differential by sex (66% for females and 79% for males) and race (51% for blacks, 60% for whites). In bias analysis, the HR for black race was attenuated from 2.81 (95%CI:1.36-5.80) to 1.23 (95%CI:1.14-1.33). The estimate for hypertension was statistically significant only in bias analysis. Estimates and inferences for the other covariates were modestly different. Differential misclassification may lead to important biases of risk factors, but can be recognized and addressed using probabilistic bias analyses.

There is a need for preclinical testing systems that predict the efficacy, safety and pharmacokinetics of cancer therapies better than existing in vitro and in vivo animal models. An approach to the development of predictive in vitro systems is to more closely recapitulate the cellular and spatial complexity of human cancers. One limitation of using current in vitro systems to model cancers is the lack of an appropriately large volume to accommodate the development of this complexity over time. To address this limitation, we have designed and constructed a novel flow-perfusion bioreactor system that can support large-volume, engineered tissue comprised of multicellular cancer surrogates by modifying current microfluidic devices. Key features of this technology are a three-dimensional (3D) volume (1.2 cm3 ) that has greater tissue thickness than is utilized in existing microfluidic systems and the ability to perfuse the volume, enabling the development of realistic tumour geometry. The constructs were fabricated by infiltrating porous carbon foams with an extracellular matrix (ECM) hydrogel and engineering through-microchannels. The carbon foam structurally supported the hydrogel and microchannel patency for up to 161 h. The ECM hydrogel was shown to adhere to the carbon foam and polydimethylsiloxane flow chamber, which housed the hydrogel-foam construct, when surfaces were coated with glutaraldehyde (carbon foam) and nitric acid (polydimethylsiloxane). Additionally, the viability of breast cancer cells and fibroblasts was higher in the presence of perfused microchannels in comparison to similar preparations without microchannels or perfusion. Therefore, the flow-perfusion bioreactor system supports cell viability in volume and stromal contexts that are physiologically-relevant. Copyright © 2015 John Wiley & Sons, Ltd.

Ninety-two young adults were randomly assigned to watch two episodes of The OCD Project, a reality television program depicting the treatment of obsessive-compulsive disorder using exposure therapy, or two episodes of another reality television program (Big Brother). Participants in The OCD Project condition (n = 35) endorsed significantly fewer negative beliefs about exposure therapy than participants in the Big Brother condition (n = 42). Participants' obsessivecompulsive disorder symptoms did not moderate the beneficial effects of watching The OCD Project. These results provide preliminary evidence that reality television programs can have a modest psychoeducational benefit and might be used to change attitudes about mental health problems and their treatment.Keywords: obsessive-compulsive disorder; exposure therapy; psychoeducation; reality televisionReality television covers a wide range of situations from surviving in the deserted wilderness while competing for money to choosing a wedding dress (e.g., Burnett, 2000; Sorrenti, 2007). Recently, reality television has also begun to address mental disorders and their treatment on programs such as The OCD Project, Hoarders, and Intervention (Benz, 2005; Klasey, 2009; Reed, 2010). As mental health-related programming increases, it reaches more lay individuals who may have been otherwise unaware of phenomena such as obsessions, compulsions, and exposure therapy. The high 12-month prevalence of obsessive-compulsive disorder (OCD), estimated to be about 1.0% (Kessler, Chiu, Demler, Merikangas, & Walters, 2005), suggests that a substantial number of viewers of reality television programs such as The OCD Project meet criteria for the disorder themselves or have a loved one who does. As such, reality television programs may provide a valuable source of education about the therapeutic benefits of exposure therapy (also known as exposure and ritual [or response] prevention), the recommended first-line treatment for OCD (National Institute for Health and Care Excellence, 2011). Unfortunately, empirical research has not examined the effects of viewing television programs such as The OCD Project on attitudes toward exposure therapy. This study was conducted to address this issue.Reality television has the potential to be an effective dissemination tool (Tolin, 2011). Viewers have the opportunity to better understand the rationale and delivery of exposure therapy and can observe the benefits of this approach to patients who receive it. In addition, therapists are generally portrayed as knowledgeable, helpful, and empathic, which may encourage potential patients to seek treatment. Lastly, viewers likely include individuals with clinically significant symptoms who are at different stages of readiness to change (Prochaska, DiClemente, & Norcross, 1993). Viewing a reality television program might increase viewers' awareness of their symptoms and motivation to change. For example, one viewer wrote,"The OCD Project" unequivocally saved my life . . . I was overwhelmed to know that I wasn't alone and that there was hope. It has now been a year since I began therapy . . . It has been tremendous. My path to healing began with [this] show. (Tolin, 2011)Alternatively, it is possible that reality television programs such as The OCD Project might have negative effects. Because these shows are created for purposes of entertainment rather than dissemination of accurate information about mental disorders and their treatment, they are often sensational and focus largely on more extreme aspects of therapy and on individuals with severe psychopathology (Tolin, 2011). Television episodes may highlight negative patient reactions to "extreme" exposure tasks, even when such reactions are atypical, thereby prompting concerns that exposure therapy is intolerable and unethical. Reality television risks sensationalizing mental disorders and their treatment and promoting negative beliefs by depicting these phenomena in oversimplified or inaccurate terms. …

Preliminary evidence has demonstrated the benefits of targeting self-compassion in the treatment of posttraumatic stress disorder (PTSD). However, survivors of childhood maltreatment may present with unique challenges that compromise the effectiveness of these and other PTSD treatments. Specifically, childhood maltreatment victims often exhibit a marked fear and active resistance of self-kindness and warmth (i.e., fear of self-compassion). Victims may also attempt to control distressing internal experiences in a way that hinders engagement in value-based actions (i.e., psychological inflexibility). Research suggests that psychological inflexibility exacerbates the negative effects of fear of self-compassion. The present study expanded on previous research by examining the relations among childhood maltreatment, fear of self-compassion, psychological inflexibility, and PTSD symptom severity in 288 college women. As expected, moderate to severe levels of childhood maltreatment were associated with greater fear of self-compassion, psychological inflexibility, and PTSD symptom severity compared to minimal or no childhood maltreatment. A mediation analysis showed that childhood maltreatment had a significant indirect effect on PTSD symptom severity via fear of self-compassion, although a conditional process analysis did not support psychological inflexibility as a moderator of this indirect effect. A post hoc multiple mediator analysis showed a significant indirect effect of childhood maltreatment on PTSD symptom severity via psychological inflexibility, but not fear of self-compassion. These findings highlight the importance of addressing fear of self-compassion and psychological inflexibility as barriers to treatment for female survivors of childhood maltreatment.

A design methodology is proposed for electronic systems powered by energy harvesting. The methodology first considers the operating environment. It then evaluates the supply-side (the attributes of the harvester), the demand-side (the engineering application or load which receives and uses the converted power), and the power conditioning needed between supply and demand. A test case is presented in which the vibrations of an electromagnetic device are harvested, converted, and used to power a wireless sensor node. Such a node is being used for the condition based monitoring of manufacturing equipment.

The association between subclinical cardiovascular disease (SCVD) and cognitive function is well established, however, current tools for addressing subgroups of SCVD have focused on the overall burden of disease. Identifying risky combinations of characteristics may lead to a better understanding of pathophysiologic changes that underlie cognitive decline. Participants included 5,072 older adults from the Cardiovascular Health Study without cardiovascular disease at baseline and followed for 6 years. Using latent class analysis, we identified cardiovascular damage phenotypes based on vascular (internal intima-media thickness, ankle-arm index, white matter grade, and brain infarctions), cardiac (major echocardiogram abnormalities, ST2, and N-terminal pro-brain natriuretic peptide) and inflammatory (interleukin-6, galectin-3, and cystatin C) markers. Using the maximum probability assignment rule, participants were assigned to phenotypes based on the highest posterior probability of membership. We used adjusted linear mixed effects models to evaluate the association between phenotype and cognitive decline, measured annually using the Modified Mini-Mental State Exam. The analysis yielded 5 prevalent phenotypes: healthy (65%), cardiac (10%), inflammatory (10%), multisystem morbidity (11%), and vascular (4%). The vascular phenotype had the greatest rate of decline at 0.88 points per year (95% CI= -1.33, -0.44), followed by the multisystem morbidity phenotype (β=-0.72, 95% CI= -1.07, -0.38), the inflammatory phenotype (β=-0.67, 95% CI= -0.95, -0.38), and the cardiac phenotype (β=-0.45, 95% CI= -0.70, -0.21) compared to the healthy phenotype. Among patterns of cardiovascular damage, vascular damage appears to have the greatest influence on cognitive decline. Identification of these phenotypes may give rise to more informed clinical interventions.

A passively self-tuning resonator configuration is presented in this study. Three different prototype beam–mass systems were built and tested and all successfully displayed passive self-tuning behavior when driven by vibrations at frequencies ranging from 45 to 140 Hz and accelerations ranging from 0.007 to 2 g . All three systems were able to achieve tuning within their operating regime when driven at a single frequency, as well as maintain a tuned condition as frequency was stepped up or down, demonstrating a bandwidth between 6 and 40 Hz. One application of such a passively self-tuning system is in vibration energy harvesting, where it is critical for performance that the harvester device resonance frequency matches the input vibration frequency, yet the input frequency may change over time and is not known a priori. The self-tuning resonator demonstrated in this paper can enable the energy harvesting system to adjust to the varying input frequencies and thereby increase the energy harvested over time.

Manufacture of piezoelectric energy harvesters typically assumes bulk piezoelectric material for the transducer until the reduction in size of the device prevents this. However when designing piezoelectric harvesters, the complete system must be taken into account including the transducer, power circuit, and battery, as these will impose restrictions on what can be achieved. Therefore a comparison between MEMS and meso-scale piezoelectric energy harvesting systems using a fully parametrised model is required. The comparison was restricted to a piezoelectric beam with a mass at the end connected to a single supply pre-biasing circuit to provide the optimal damping force and rectification. A buck converter was used to transfer extracted energy to a 1.5V battery. The results indicate that for devices with a volume side length less than 16.25 mm, no device using meso-scale properties can be made to resonant at 100 Hz or less due to the length and stiffness of the beam. Whereas above this limit, the voltage required to damp devices with MEMS scale properties causes a breakdown in the dielectric. We present a comparison of the theoretical limits of MEMS and meso-scale piezoelectric harvesters to provide design insight for future devices to maximise power generation.

Three dimensional (3D) culture is a more physiologically relevant method to model cell behavior in vitro than two dimensional culture. Carcinomas, including breast carcinomas, are complex 3D tissues composed of cancer epithelial cells and stromal components, including fibroblasts and extracellular matrix (ECM). Yet most in vitro models of breast carcinoma consist only of cancer epithelial cells, omitting the stroma and, therefore, the 3D architecture of a tumor in vivo. Appropriate 3D modeling of carcinoma is important for accurate understanding of tumor biology, behavior, and response to therapy. However, the duration of culture and volume of 3D models is limited by the availability of oxygen and nutrients within the culture. Herein, we demonstrate a method in which breast carcinoma epithelial cells and stromal fibroblasts are incorporated into ECM to generate a 3D breast cancer surrogate that includes stroma and can be cultured as a solid 3D structure or by using a perfusion bioreactor system to deliver oxygen and nutrients. Following setup and an initial growth period, surrogates can be used for preclinical drug testing. Alternatively, the cellular and matrix components of the surrogate can be modified to address a variety of biological questions. After culture, surrogates are fixed and processed to paraffin, in a manner similar to the handling of clinical breast carcinoma specimens, for evaluation of parameters of interest. The evaluation of one such parameter, the density of cells present, is explained, where ImageJ and CellProfiler image analysis software systems are applied to photomicrographs of histologic sections of surrogates to quantify the number of nucleated cells per area. This can be used as an indicator of the change in cell number over time or the change in cell number resulting from varying growth conditions and treatments.

This paper presents a complete optimization of a piezoelectric vibration energy harvesting system, including a piezoelectric transducer, a power conditioning circuit with full semiconductor device models, a battery and passive components. To the authors awareness, this is the first time and all of these elements have been integrated into one optimization. The optimization is done within a framework, which models the combined mechanical and electrical elements of a complete piezoelectric vibration energy harvesting system. To realize the optimization, an optimal electrical damping is achieved using a single-supply pre-biasing circuit with a buck converter to charge the battery. The model is implemented in MATLAB and verified in SPICE. The results of the full system model are used to find the mechanical and electrical system parameters required to maximize the power output. The model, therefore, yields the upper bound of the output power and the system effectiveness of complete piezoelectric energy harvesting systems and, hence, provides both a benchmark for assessing the effectiveness of existing harvesters and a framework to design the optimized harvesters. It is also shown that the increased acceleration does not always result in increased power generation as a larger damping force is required, forcing a geometry change of the harvester to avoid exceeding the piezoelectric breakdown voltage. Similarly, increasing available volume may not result in the increased power generation because of the difficulty of resonating the beam at certain frequencies whilst utilizing the entire volume. A maximum system effectiveness of 48% is shown to be achievable at 100 Hz for a 3.38-cm3 generator.

This paper answers the often asked, and until now inadequately answered, question of which MEMS compatible transducer type achieves the best power density in an energy harvesting system. This question is usually poorly answered because of the number of variables which must be taken into account and the multi-domain nature of the modelling and optimisation. The work here includes models of the mechanics, transducer and the power processing circuits (e.g. rectification and battery management) which in turn include detailed semiconductor models. It is shown that electrostatic harvesters perform better than piezoelectric harvesters at low accelerations, due to lower energy losses, and the reverse is generally true at high accelerations. At very high accelerations using MEMS-scale devices the dielectric breakdown limit in piezoelectric energy harvesters severely decreases their performance thus electrostatics are again preferred. Using the insights gained in this comparison, the optimal transduction mechanism can be chosen as a function of harvesting operating frequency, acceleration and device size.

There is a need for preclinical testing systems that predict the efficacy, safety and pharmacokinetics of cancer therapies better than existing in vitro and in vivo animal models. An approach to the development of predictive in vitro systems is to more closely recapitulate the cellular and spatial complexity of human cancers. One limitation of using current in vitro systems to model cancers is the lack of an appropriately large volume to accommodate the development of this complexity over time. To address this limitation, we have designed and constructed a novel flow–perfusion bioreactor system that can support large-volume, engineered tissue comprised of multicellular cancer surrogates by modifying current microfluidic devices. Key features of this technology are a three-dimensional (3D) volume (1.2 cm3) that has greater tissue thickness than is utilized in existing microfluidic systems and the ability to perfuse the volume, enabling the development of realistic tumour geometry. The constructs were fabricated by infiltrating porous carbon foams with an extracellular matrix (ECM) hydrogel and engineering through-microchannels. The carbon foam structurally supported the hydrogel and microchannel patency for up to 161 h. The ECM hydrogel was shown to adhere to the carbon foam and polydimethylsiloxane flow chamber, which housed the hydrogel–foam construct, when surfaces were coated with glutaraldehyde (carbon foam) and nitric acid (polydimethyl-siloxane). Additionally, the viability of breast cancer cells and fibroblasts was higher in the presence of perfused microchannels in comparison to similar preparations without microchannels or perfusion. Therefore, the flow–perfusion bioreactor system supports cell viability in volume and stromal contexts that are physiologically-relevant.

Real world systems rarely vibrate at a single resonance frequency and the frequencies drift over time. Tunable devices exist, but generally need additional energy to achieve frequency adaptation. This means that the benefits in power output from this tuning need to be large enough to power the mechanism itself. Passively self-tuning systems go into resonance without requiring active control. This paper focuses on a passively self-tuning system with a proof mass that can slide freely along a clamped-clamped beam. Under external vibration, the slider moves along the beam until the system goes into resonance. A proof-of-concept design is introduced using either a copper or a steel beam and a 3D-printed ABS thermoplastic proof mass. Successful self-tuning is demonstrated in both cases. The frequencies range from 80 – 140 Hz at accelerations as low as 0.007 g rms. Results show the resonance of the beam and the position of the slider along the beam with time. Furthermore, the dynamic magnification and the proof mass position at resonance are discussed, together with the inherent non-linearities of double-clamped beam resonators. The findings support the hypothesis that the effect of the ratio between proof mass and beam mass outweighs the Duffing spring stiffening effects.

This work presents an integration approach towards manufacturing a MEMS piezoelectric vibration energy harvester and an electrochemical capacitor on the same substrate. Vibration energy harvesters have been fabricated to resonate at low frequencies, matching ambient vibrations found abundantly in buildings. For cost-effective resonance tuning, a direct write dispenser printer can be used to print additional mass at the tips of the beams, and is also used to deposit a capacitor in the open space surrounding the beam. The implementation of a power supply on a single platform is of great value especially for autonomous wireless sensors with long lifetime and small device volume requirements.

We present a design study highlighting our recent technological developments that will enable the implementation of autonomous wireless sensor networks for home healthcare monitoring systems. We outline the power requirements for a commercially available implantable glucose sensor which transmits measurements to an external wireless sensor node embedded in the home. A network of these sensor nodes will relay the data to a base station, such as a computer with internet connection, which will record and report this data to the user. We explore the feasibility of powering these sensors using energy scavenging from both body temperature gradients and vibrations in the home, and discuss our developments in energy storage and low power consuming hardware.

Vibrational energy scavenging using piezoelectric material is a viable method to provide sufficient energy for low-power wireless sensor networks. The applications for such devices in hospital settings as well as in vivo are abundant. Current devices are limited by both their design and material selection. This paper will address optimizing the design of microscale devices by showing how the device strains under input vibrations are directly proportional to its power output, and by proposing alternate designs which increase the strain distribution over more of the device volume. Finite element modeling (ANSYS®) was used to determine the strain distribution in a cantilever, modified cantilever, trapezoid, and spiral shaped piezoelectric microscale energy scavenging system. The increase in strain under uniform acceleration was determined to be 0, 29.2, 37.8, and 87.0%, respectively, over that of a simple cantilever.

Switching interface circuits employed with piezoelectric energy harvesters can increase the electrical damping considerably over that achievable with passive rectifiers. We show that a piezoelectric harvester coupled to certain types of switching circuits becomes a Coulomb-damped resonant generator. This allows analysis of such harvester systems within a well-known framework and, subject to practical constraints, allows the optimal electrical damping to be achieved. In the piezoelectric pre-biasing technique, the Coulomb damping is set by a pre-bias voltage whose optimal value is derived as a function of piezoelectric harvester parameters.

Micro-fabricated piezoelectric vibration energy harvesters with resonance frequencies of 31–232 Hz are characterized and deployed for testing on ambient vibration sources in the machine room of a large building. A survey of 23 ambient vibration sources in the machine room is presented. A model is developed which uses a discretization method to accept measured arbitrary acceleration data as an input and gives harvester response as output. The modeled and measured output from the energy harvesters is compared for both vibrometer and ambient vibration sources. The energy harvesters produced up to 43 nWrms g−2 on a laboratory vibrometer and 10 nW g−2 on ambient vibration sources typically in large buildings.