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Combining optics and microfluidics to create a portable optofluidic photonic crystal (PhC) biosensor is an approach with promising applications in the fields of counter-terrorism, agricultural sciences, and health sciences. Presented here are fabrication processes of a gallium nitride (GaN)-based PhC biosensor with a resonance-enhanced fluorescence detection mechanism that shows potential for meeting the single molecule detection requirements of these application areas. GaN is being targeted as the photonic crystal slab material for two main reasons: its transparency in the visible spectral range, within which the excitation and emission wavelengths of the commercial fluorescent-labeling dyes fall, and its intrinsic thermal stability which provides an increased flexibility of operating in different environments. Optical modeling efforts indicate a 25-fold enhancement of the fluorescent emission in this portable fluorescentbased PhC biosensor.
Quantum dots play a promising role in the development of novel optical and biosensing devices. In this study, we investigated steady state and time-dependent luminescence properties of InGaP/ZnS core/shell colloidal quantum dots in a solution phase at room temperature. The steady state experiments exhibited an emission maximum at 650 nm with full width at half maximum of ~ 85 nm, and strong first-excitonic absorption peak at 600 nm. The time-resolved luminescence measurements depicted a bi-exponential decay profile with lifetimes of τ1 ~ 47 ns and τ2 ~ 142 ns at the emission maximum. Additionally, luminescence quenching and lifetime reduction due to resonance energy transfer between the quantum dot and an absorber are demonstrated. Our results support the plausibility of using these InGaP quantum dots as an effective alternative to highly toxic conventional Cd or Pb based colloidal quantum dots for biological applications.
Detection of important biological molecules using surface-enhanced Raman scattering (SERS) has become widely used because of the highly sensitive and label free approach offered by SERS as well as the low cytotoxic response from some SERS substrates. Gold nanoparticles are commonly used in SERS studies; however, the inherent instability of these metal nanostructures in solution adversely influences the reproducibility and quantitative nature of these measurements. Furthermore, the metal surface often denatures biomolecules upon their direct interaction. To combat this incompatibility and improve optical stability, gold nanoparticles have been encapsulated in silica shells. These Au@SiO2 nanostructures have been used extensively in cellular studies, but their SERS capabilities are generally limited to uses that include silica-entrapped SERS reporter molecules rather than direct SERS detection. This work focuses on combating these limitations via the fabrication of Au@SiO2 nanoparticles with porous silica membranes for the direct detection of target molecules in solution. Gold nanoparticles have been designed and coated with a variety of silica morphologies and subsequently interrogated using extinction spectroscopy and SERS. It will be revealed that these gold nanoparticles entrapped in silica membranes serve as optically stable substrates for the quantitative and direct detection of target molecules. These advances in nanomaterial fabrication are envisioned to impact both fundamental and applied studies in a variety of research areas including catalysis, separations, and spectroscopy.
We develop rapid chemical vapor sensors and micro gas chromatography (μGC) analyzers based on the optofluidic ring resonator (OFRR). An OFRR is a micro-sized thin-walled glass capillary; the circular cross-section of the capillary acts as an optical ring resonator while the whispering gallery modes or circulating waveguide modes (WGMs) supported by the ring resonator interact with the vapor samples passing through the capillary. The OFRR interior surface is coated with a vapor-sensitive polymer. The analyte and polymer interaction causes the polymer refractive index (RI) and the thickness to change, which is detected as a WGM spectral shift. Owing to the excellent fluidics, the OFRR vapor sensor exhibits sub-second detection and recovery time with a flow rate of 1 mL/min. On-column separation and detection in the OFRR based μGC system is also demonstrated, showing efficient separation of vapor mixtures and presenting highly reproducible retention time for the individual analyte. Compared to the conventional GC system, the OFRR μGC has the advantage of small size, rapid response, and high selectivity over a short length of column.
This work proves that a 1-D porous silicon (PSi) sensor is capable of monitoring the optical changes in a polyacrylamide (PAAm) hydrogel that correlate with swelling capacity. The PSi device was impregnated with PAAm hydrogel with varying crosslinking density and total solids. The optical response of the PSi sensor was utilized to distinguish the changes in refractive index of hydrogels with varying cross-linking densities. Refractive index values calculated by the composite hydrogel-PSi sensor response agree well (≤1% difference) with values measured using a bench-top refractometer. This work serves to build a foundation for creating a composite biochemical-responsive hydrogel-PSi sensor in which competitive binding of a target analyte would cause a reduction in hydrogel cross-linking density. Long-term goals of this work are to exploit the volume sensitivity of a PSi sensor and leverage the added optical response of the responsive hydrogel to increase target detection sensitivity in an affinity based biosensor.
Traditional decision rules have limitations when a new technology is less effective and less costly than a comparator. We propose a new probabilistic decision framework to examine non-inferiority in effectiveness and net monetary benefit (NMB) simultaneously. We illustrate this framework using the example of repetitive transcranial magnetic stimulation (rTMS) and electroconvulsive therapy (ECT) for treatment-resistant depression.
We modeled the quality-adjusted life-years (QALYs) associated with the new intervention (rTMS), an active control (ECT), and a placebo control, and we estimated the fraction of effectiveness preserved by the new intervention through probabilistic sensitivity analysis (PSA). We then assessed the probability of cost-effectiveness using a traditional cost-effectiveness acceptability curve (CEAC) and our new decision-making framework. In our new framework, we considered the new intervention cost-effective in each simulation of the PSA if it preserved at least 75 percent of the effectiveness of the active control (thus demonstrating non-inferiority) and had a positive NMB at a given willingness-to-pay threshold (WTP).
rTMS was less effective (i.e., associated with fewer QALYs) and less costly than ECT. The traditional CEAC approach showed that the probabilities of rTMS being cost-effective were 100 percent, 39 percent, and 14 percent at WTPs of $0, $50,000, and $100,000 per QALY gained, respectively. In the new decision framework, the probabilities of rTMS being cost-effective were reduced to 23 percent, 21 percent, and 13 percent at WTPs of $0, $50,000, and $100,000 per QALY, respectively.
This new framework provides a different perspective for decision making with considerations of both non-inferiority and WTP thresholds.
In the nearly a quarter of a century since the addition of the clinically significant distress/impairment criterion to the definition of PTSD in DSM-IV, little research has been done to examine the association of this criterion with symptom group criteria and with the numbing subgroup specifically. This study was conducted to examine these relationships in a large database of disaster survivors consistently studied across 12 different incidents of the full range of disaster typology.
Analysis was conducted on a merged database representing 1187 trauma-exposed survivors of 12 different disasters studied systematically. DSM-IV-TR criteria for disaster-related PTSD were assessed with the Diagnostic Interview Schedule.
PTSD Group C (avoidance/numbing) and numbing specifically were less common and more associated than other symptom groups with criterion F (distress/impairment). Consistently in multivariable models, group C and numbing were independently associated with criterion F. Group D (hyperarousal) was less strongly associated with criterion F. Neither group B (intrusion) nor avoidance were associated with criterion F.
In this and other studies, group C and numbing specifically have been shown to be associated with criterion F, which is consistent with the demonstration that group C and the numbing component specifically are central to the psychopathology of PTSD. The addition of the distress/impairment requirement broadly across the psychiatric diagnoses in DSM-IV added little value to PTSD symptom criteria. Future revisions of diagnostic criteria may benefit by carefully considering these findings to possibly re-include a prominent numbing symptom section.
India has the second largest number of people with type 2 diabetes (T2D) globally. Epidemiological evidence indicates that consumption of white rice is positively associated with T2D risk, while intake of brown rice is inversely associated. Thus, we explored the effect of substituting brown rice for white rice on T2D risk factors among adults in urban South India. A total of 166 overweight (BMI ≥ 23 kg/m2) adults aged 25–65 years were enrolled in a randomised cross-over trial in Chennai, India. Interventions were a parboiled brown rice or white rice regimen providing two ad libitum meals/d, 6 d/week for 3 months with a 2-week washout period. Primary outcomes were blood glucose, insulin, glycosylated Hb (HbA1c), insulin resistance (homeostasis model assessment of insulin resistance) and lipids. High-sensitivity C-reactive protein (hs-CRP) was a secondary outcome. We did not observe significant between-group differences for primary outcomes among all participants. However, a significant reduction in HbA1c was observed in the brown rice group among participants with the metabolic syndrome (−0·18 (se 0·08) %) relative to those without the metabolic syndrome (0·05 (se 0·05) %) (P-for-heterogeneity = 0·02). Improvements in HbA1c, total and LDL-cholesterol were observed in the brown rice group among participants with a BMI ≥ 25 kg/m2 compared with those with a BMI < 25 kg/m2 (P-for-heterogeneity < 0·05). We observed a smaller increase in hs-CRP in the brown (0·03 (sd 2·12) mg/l) compared with white rice group (0·63 (sd 2·35) mg/l) (P = 0·04). In conclusion, substituting brown rice for white rice showed a potential benefit on HbA1c among participants with the metabolic syndrome and an elevated BMI. A small benefit on inflammation was also observed.
The authors demonstrate that gold-binding peptides displayed on the outer membrane of Escherichia coli enhance bioelectrochemical charge transfer by binding gold nanoparticles. Microbial fuel cells were run with different gold-binding peptides displayed and with different nanoparticle sizes, and the results were correlated with transmission electron microscopy (TEM) imaging of nanoparticle binding. When a gold-binding peptide is displayed and 5 nm gold nanoparticles are present, up to 4× power generation over E. coli not displaying a gold-binding peptide is observed. While an enhanced current is observed using the previously published M6G9, the largest enhancement is observed when a new longer peptide named M9G18 is used.
Habitat prioritization and corridor restoration are important steps for reconnecting fragmented habitats and species populations, and spatial modelling approaches are useful in identifying suitable habitat for elusive tropical rainforest mammals. The Endangered Bornean banteng Bos javanicus lowi, a wild bovid endemic to Borneo, occurs in habitat that is highly fragmented as a result of extensive agricultural expansion. Based on the species’ historical distribution in Sabah (Malaysia), we conducted camera-trap surveys in 14 forest reserves during 2011–2016. To assess suitable habitat for the banteng we used a presence-only maximum entropy (MaxEnt) approach with 11 spatial predictors, including climate, infrastructure, land cover and land use, and topography variables. We performed a least-cost path analysis using Linkage Mapper, to understand the resistance to movement through the landscape. The surveys comprised a total of 44,251 nights of camera trapping. We recorded banteng presence in 11 forest reserves. Key spatial predictors deemed to be important in predicting suitable habitat included soil associations (52.6%), distance to intact and logged forests (11.8%), precipitation in the driest quarter (10.8%), distance to agro-forest and regenerating forest (5.7%), and distance to oil palm plantations (5.1%). Circa 11% of Sabah had suitable habitat (7,719 km2), of which 12.2% was in protected forests, 60.4% was in production forests and 27.4% was in other areas. The least-cost path model predicted 21 linkages and a relatively high movement resistance between core habitats. Our models provide information about key habitat and movement resistance for bantengs through the landscape, which is crucial for constructive conservation strategies and land-use planning.
Ca and dairy product intakes may be inversely associated with all-cause and cause-specific mortality, and non-Ca components of dairy products, such as insulin-like growth factor-1, may be independently associated with mortality. We investigated associations of Ca and dairy product intakes with all-cause, all-cancer, colorectal cancer (CRC) and CHD mortality among 35 221 55- to 69-year-old women in the prospective Iowa Women’s Health Study, who were cancer-free in 1986. We assessed diet using a Willett FFQ, and associations using multivariable Cox proportional hazards regression. We estimated residuals from linear regression models of dairy products with dietary Ca to investigate total and specific dairy products independent of their Ca content. Through 2012, 18 687 participants died, including 4665 from cancer (including 574 from CRC) and 3603 from CHD. For those in the highest relative to the lowest quintiles of intake, the multivariable-adjusted hazard ratios (HR) and 95 % CI for total Ca (dietary plus supplemental) were 0·88 (0·83, 0·93; P trend=0·001) for all-cause mortality, 0·91 (0·81, 1·02; P trend=0·34) for all-cancer mortality, 0·60 (0·43, 0·83; P trend=0·002) for CRC mortality and 0·73 (0·64, 0·83; P trend <0·0001) for CHD mortality. The corresponding HR for associations of whole milk, whole milk residuals, and low-/non-fat milk residuals with all-cause mortality were 1·20 (95 % CI 1·13, 1·27), 1·20 (95 % CI 1·13, 1·28) and 0·91 (95 % CI 0·86, 0·96), respectively. These results suggest that Ca may be associated with lower risk of all-cause, CRC and CHD mortality, and that non-Ca components of milk may be independently associated with mortality.
OBJECTIVES/SPECIFIC AIMS: Intensive lifestyle change (e.g., the Diabetes Prevention Program) and metformin reduce type 2 diabetes risk among patients with prediabetes. However, real-world uptake remains low. Shared decision-making (SDM) may increase awareness and help patients select and follow through with informed options for diabetes prevention that are aligned with their preferences.The objective was to test the effectiveness of a prediabetes SDM intervention. METHODS/STUDY POPULATION: This was a cluster-randomized controlled trial in 20 primary care clinics within a large regional health system. Participants were overweight/obese adults with prediabetes (BMI>24 kg/m2 and HbA1c 5.7-6.4%) were enrolled from 10 SDM intervention clinics. Propensity score matching was used to identify control patients from 10 usual care clinics.Intervention clinic patients were invited to participate in a face-to-face SDM visit with a pharmacist who used a decision aid (DA) to describe prediabetes and four possible options for diabetes prevention; DPP, DPP +/− metformin, metformin only, or usual care. RESULTS/ANTICIPATED RESULTS: Uptake of DPP and/or metformin was higher among SDM participants (n=351) than controls receiving usual care (n = 1,028; 38% vs. 2%, p<.001). At 12-months follow-up, adjusted weight loss (lbs.) was greater among SDM participants than controls (−5.3 vs. −0.2, p < .001). DISCUSSION/SIGNIFICANCE OF IMPACT: A prediabetes SDM intervention led by pharmacists increased patient engagement in evidence-based options for diabetes prevention and was associated with significantly greater uptake of DPP and/or metformin at 4-months and weight loss at 12-months. Prediabetes SDM may be a promising approach to enhance prevention efforts among patients at increased risk.
Many seed quality tests are conducted by first randomly assigning seeds into replicates of a given size. The replicate results are then used to check whether or not any problems occur in the realization of the test. The two main tools developed for this verification are the ratio of the observed variance of the replicate results to a theoretical variance and the tolerance for the range of the results. In this paper, we derive the theoretical distribution and its related properties of the sequence of numbers of seeds with a given quality attribute present in the replicates. From these theoretical results, we revisit the two quality checking tools widely used for the germination test. We show a precaution to be taken when relying on the variance ratio to check for under- or over-dispersion of the replicate results. This has led to the development of tables providing credible intervals of the variance ratio. The International Seed Testing Association tolerance tables for the range of the results are also compared with tolerances computed from the exact theoretical distribution of the range, leading us to recommend a revision of these tables.
Childhood maltreatment is one of the strongest predictors of adulthood depression and alterations to circulating levels of inflammatory markers is one putative mechanism mediating risk or resilience.
To determine the effects of childhood maltreatment on circulating levels of 41 inflammatory markers in healthy individuals and those with a major depressive disorder (MDD) diagnosis.
We investigated the association of childhood maltreatment with levels of 41 inflammatory markers in two groups, 164 patients with MDD and 301 controls, using multiplex electrochemiluminescence methods applied to blood serum.
Childhood maltreatment was not associated with altered inflammatory markers in either group after multiple testing correction. Body mass index (BMI) exerted strong effects on interleukin-6 and C-reactive protein levels in those with MDD.
Childhood maltreatment did not exert effects on inflammatory marker levels in either the participants with MDD or the control group in our study. Our results instead highlight the more pertinent influence of BMI.
Declaration of interest
D.A.C. and H.W. work for Eli Lilly Inc. R.N. has received speaker fees from Sunovion, Jansen and Lundbeck. G.B. has received consultancy fees and funding from Eli Lilly. R.H.M.-W. has received consultancy fees or has a financial relationship with AstraZeneca, Bristol-Myers Squibb, Cyberonics, Eli Lilly, Ferrer, Janssen-Cilag, Lundbeck, MyTomorrows, Otsuka, Pfizer, Pulse, Roche, Servier, SPIMACO and Sunovian. I.M.A. has received consultancy fees or has a financial relationship with Alkermes, Lundbeck, Lundbeck/Otsuka, and Servier. S.W. has sat on an advisory board for Sunovion, Allergan and has received speaker fees from Astra Zeneca. A.H.Y. has received honoraria for speaking from Astra Zeneca, Lundbeck, Eli Lilly, Sunovion; honoraria for consulting from Allergan, Livanova and Lundbeck, Sunovion, Janssen; and research grant support from Janssen. A.J.C. has received honoraria for speaking from Astra Zeneca, honoraria for consulting with Allergan, Livanova and Lundbeck and research grant support from Lundbeck.
Background: Localization of intramedullary spine tumors can be difficult. Various intraoperative aids have previously been described, but have limited use due to expense, complexity, and time. Intravenous fluorescein is an inexpensive and safe drug that may be useful in the localization of such tumors. We describe a technical description of the intra-operative use of fluorescein as an aid in the localization of a intramedullary spine tumour. Methods: In this technical report, the authors present a case example of a 56 year old man presenting with a intramedullary tumor at the level of C5/6. Intra-operatively intravenous Fluorescein was administered and the Pentero microscope BLUE™ 400 feature was used to accurately identify the lesion. Multiple biopsies of the fluorescent tissue were taken. Results: After 10 cardiac cycles the fluorescent coloring was isolated to what was thought to be the intramedullary lesion. Our myelotomy was made based on the uptake of this fluorescent coloring and multiple biopsies were taken. Final pathology confirmed this tissue was consistent with a high grade glioma. Conclusions: The use of intravenous fluorescein was a valuable aid in localizing the lesion and minimizing the size of our myelotomy. The use of intravenous fluorescein to localize high grade intramedullary spinal cord tumours appears to be safe, accurate, and inexpensive.
We report the utility of whole-genome sequencing (WGS) conducted in a clinically relevant time frame (ie, sufficient for guiding management decision), in managing a Streptococcus pyogenes outbreak, and present a comparison of its performance with emm typing.
A 2,000-bed tertiary-care psychiatric hospital.
Active surveillance was conducted to identify new cases of S. pyogenes. WGS guided targeted epidemiological investigations, and infection control measures were implemented. Single-nucleotide polymorphism (SNP)–based genome phylogeny, emm typing, and multilocus sequence typing (MLST) were performed. We compared the ability of WGS and emm typing to correctly identify person-to-person transmission and to guide the management of the outbreak.
The study included 204 patients and 152 staff. We identified 35 patients and 2 staff members with S. pyogenes. WGS revealed polyclonal S. pyogenes infections with 3 genetically distinct phylogenetic clusters (C1–C3). Cluster C1 isolates were all emm type 4, sequence type 915 and had pairwise SNP differences of 0–5, which suggested recent person-to-person transmissions. Epidemiological investigation revealed that cluster C1 was mediated by dermal colonization and transmission of S. pyogenes in a male residential ward. Clusters C2 and C3 were genomically diverse, with pairwise SNP differences of 21–45 and 26–58, and emm 11 and mostly emm120, respectively. Clusters C2 and C3, which may have been considered person-to-person transmissions by emm typing, were shown by WGS to be unlikely by integrating pairwise SNP differences with epidemiology.
WGS had higher resolution than emm typing in identifying clusters with recent and ongoing person-to-person transmissions, which allowed implementation of targeted intervention to control the outbreak.
Introduction: Approximately 50% of patients discharged from the Emergency Department (ED) after syncope have no cause found. Long-term outcomes among syncope patients are not well studied, to guide physicians regarding outpatient testing and follow-up. The objective of this study was to conduct a systematic review for long-term (one year) outcomes among ED patients with syncope. We aim to use the results of this review to guide us in prospective analysis of one year outcomes with our large database of syncope patients. Methods: We searched Cochrane Central Register of Controlled Trials, Medline and Medline in Process, PubMed, Embase, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) from the inception to June, 2017. We included studies that reported long-term outcomes among adult ED patients (16 years or older) with syncope. We excluded studies on pediatric patients, and studies that included syncope mimickers: pre-syncope, seizure, intoxication, loss of consciousness after head trauma. We also excluded case reports, letters to the editor and review articles. Outcomes included death, syncope recurrence requiring hospitalization, arrhythmias and procedural interventions for arrhythmias. We selected articles based on title and abstract review during phase-1 and conducted full article review during phase-2. Meta-analysis was performed by pooling the outcomes using random effects model (RevMan v.5.3; Cochrane Collaboration). Results: Initial literature search generated 2094 articles after duplicate removal. 50 articles remained after phase-1 (=0.85) and 16 articles were included in the systematic review after phase-2 (=0.86). The 16 included studies enrolled a total of 44,755 patients. Pooled analysis at 1-year follow-up showed the following outcomes: 7% mortality; 14% recurrence of syncope requiring hospitalization; one study reported that 0.6% of patients had a pacemaker inserted; and two studies reported 0.8 11.5% of patients suffered new arrhythmias. Conclusion: An important proportion of ED patients with syncope suffer outcomes at 1-year. Appropriate follow-up is needed to prevent long-term adverse outcomes. Further prospective research to identify patients at risk for long-term important cardiac outcomes and death is needed.
To develop an artificial intelligence (AI)-based algorithm which can automatically detect food items from images acquired by an egocentric wearable camera for dietary assessment.
To study human diet and lifestyle, large sets of egocentric images were acquired using a wearable device, called eButton, from free-living individuals. Three thousand nine hundred images containing real-world activities, which formed eButton data set 1, were manually selected from thirty subjects. eButton data set 2 contained 29 515 images acquired from a research participant in a week-long unrestricted recording. They included both food- and non-food-related real-life activities, such as dining at both home and restaurants, cooking, shopping, gardening, housekeeping chores, taking classes, gym exercise, etc. All images in these data sets were classified as food/non-food images based on their tags generated by a convolutional neural network.
A cross data-set test was conducted on eButton data set 1. The overall accuracy of food detection was 91·5 and 86·4 %, respectively, when one-half of data set 1 was used for training and the other half for testing. For eButton data set 2, 74·0 % sensitivity and 87·0 % specificity were obtained if both ‘food’ and ‘drink’ were considered as food images. Alternatively, if only ‘food’ items were considered, the sensitivity and specificity reached 85·0 and 85·8 %, respectively.
The AI technology can automatically detect foods from low-quality, wearable camera-acquired real-world egocentric images with reasonable accuracy, reducing both the burden of data processing and privacy concerns.