Salve Regina University

Multiplexed biomarker protein detection holds unrealized promise for clinical cancer diagnostics due to lack of suitable measurement devices and lack of rigorously validated protein panels. Here we report an ultrasensitive electrochemical microfluidic array optimized to measure a four-protein panel of biomarker proteins, and we validate the protein panel for accurate oral cancer diagnostics. Unprecedented ultralow detection into the 5-50 fg·mL(-1) range was achieved for simultaneous measurement of proteins interleukin 6 (IL-6), IL-8, vascular endothelial growth factor (VEGF), and VEGF-C in diluted serum. The immunoarray achieves high sensitivity in 50 min assays by using off-line protein capture by magnetic beads carrying 400,000 enzyme labels and ~100,000 antibodies. After capture of the proteins and washing to inhibit nonspecific binding, the beads are magnetically separated and injected into the array for selective capture by antibodies on eight nanostructured sensors. Good correlations with enzyme-linked immunosorbent assays (ELISA) for protein determinations in conditioned cancer cell media confirmed the accuracy of this approach. Normalized means of the four protein levels in 78 oral cancer patient serum samples and 49 controls gave clinical sensitivity of 89% and specificity of 98% for oral cancer detection, demonstrating high diagnostic utility. The low-cost, easily fabricated immunoarray provides a rapid serum test for diagnosis and personalized therapy of oral cancer. The device is readily adaptable to clinical diagnostics of other cancers.

BACKGROUND: Rapid development of highly saturated genetic maps aids molecular breeding, which can accelerate gain per breeding cycle in woody perennial plants such as Rubus idaeus (red raspberry). Recently, robust genotyping methods based on high-throughput sequencing were developed, which provide high marker density, but result in some genotype errors and a large number of missing genotype values. Imputation can reduce the number of missing values and can correct genotyping errors, but current methods of imputation require a reference genome and thus are not an option for most species. RESULTS: Genotyping by Sequencing (GBS) was used to produce highly saturated maps for a R. idaeus pseudo-testcross progeny. While low coverage and high variance in sequencing resulted in a large number of missing values for some individuals, a novel method of imputation based on maximum likelihood marker ordering from initial marker segregation overcame the challenge of missing values, and made map construction computationally tractable. The two resulting parental maps contained 4521 and 2391 molecular markers spanning 462.7 and 376.6 cM respectively over seven linkage groups. Detection of precise genomic regions with segregation distortion was possible because of map saturation. Microsatellites (SSRs) linked these results to published maps for cross-validation and map comparison. CONCLUSIONS: GBS together with genome-independent imputation provides a rapid method for genetic map construction in any pseudo-testcross progeny. Our method of imputation estimates the correct genotype call of missing values and corrects genotyping errors that lead to inflated map size and reduced precision in marker placement. Comparison of SSRs to published R. idaeus maps showed that the linkage maps constructed with GBS and our method of imputation were robust, and marker positioning reliable. The high marker density allowed identification of genomic regions with segregation distortion in R. idaeus, which may help to identify deleterious alleles that are the basis of inbreeding depression in the species.

Static domain structures and polarization dynamics of silicon doped HfO2 are explored. The evolution of ferroelectricity as a function of Si-doping level driving the transition from paraelectricity via ferroelectricity to antiferroelectricity is investigated. Ferroelectric and antiferroelectric properties can be observed locally on the pristine, poled and electroded surfaces, providing conclusive evidence to intrinsic ferroic behavior.

Glycation is associated with several neurodegenerative disorders, including Alzheimer's disease (AD), where it potentiates the aggregation and toxicity of proteins such as β-amyloid (Aβ). Published studies support the anti-glycation and neuroprotective effects of several polyphenol-rich fruits, including berries, which are rich in anthocyanins. Herein, blackberry, black raspberry, blueberry, cranberry, red raspberry, and strawberry extracts were evaluated for: (1) total phenolic and anthocyanins contents, (2) free radical (DPPH) scavenging and reactive carbonyl species (methylglyoxal; MGO) trapping, (3) anti-glycation (using BSA-fructose and BSA-MGO models), (4) anti-Aβ aggregation (using thermal- and MGO-induced fibrillation models), and, (5) murine microglia (BV-2) neuroprotective properties. Berry crude extracts (CE) were fractionated to yield anthocyanins-free (ACF) and anthocyanins-enriched (ACE) extracts. The berry ACEs (at 100 μg/mL) showed superior free radical scavenging, reactive carbonyl species trapping, and anti-glycation effects compared to their respective ACFs. The berry ACEs (at 100 μg/mL) inhibited both thermal- and MGO-induced Aβ fibrillation. In addition, the berry ACEs (at 20 μg/mL) reduced H₂O₂-induced reactive oxygen species production, and lipopolysaccharide-induced nitric oxide species in BV-2 microglia as well as decreased H₂O₂-induced cytotoxicity and caspase-3/7 activity in BV-2 microglia. The free radical scavenging, reactive carbonyl trapping, anti-glycation, anti-Aβ fibrillation, and microglial neuroprotective effects of these berry extracts warrant further in vivo studies to evaluate their potential neuroprotective effects against AD.

A sensitive issue: Superparamagnetic particle–antibody conjugates enable detection of interleukin-8 (IL-8) in serum at a level of 1 fg mL−1 (ca. 100 aM). Ultrahigh sensitivity is facilitated by a nanostructured sensor platform coupled with secondary antibody–magnetic bead–horseradish peroxidase conjugate (Ab2–MB–HRP) with about 500 000 HRP labels (see picture).

Coincident with the global rise in concern about the spread of misinformation on social media, there has been influx of behavioral research on so-called “fake news” (fabricated or false news headlines that are presented as if legitimate) and other forms of misinformation. These studies often present participants with news content that varies on relevant dimensions (e.g., true v. false, politically consistent v. inconsistent, etc.) and ask participants to make judgments (e.g., accuracy) or choices (e.g., whether they would share it on social media). This guide is intended to help researchers navigate the unique challenges that come with this type of research. Principle among these issues is that the nature of news content that is being spread on social media (whether it is false, misleading, or true) is a moving target that reflects current affairs in the context of interest. Steps are required if one wishes to present stimuli that allow generalization from the study to the real-world phenomenon of online misinformation. Furthermore, the selection of content to include can be highly consequential for the study’s outcome, and researcher biases can easily result in biases in a stimulus set. As such, we advocate for pretesting materials and, to this end, report our own pretest of 224 recent true and false news headlines, both relating to U.S. political issues and the COVID-19 pandemic. These headlines may be of use in the short term, but, more importantly, the pretest is intended to serve as an example of best practices in a quickly evolving area of research.

ABSTRACT The links between the production of sexual subjectivity and commodity consumption exemplify how capitalism thrives through the production of plurality and difference. Tupperware-style sex-toy parties organized by and for women provide the ethnographic ground for exploring the question of how sex toys marketed in this venue incite consumer desires and reshape sexual practices. Using an interpretative approach to understanding the effects of the home-based parties as well as in-depth interviews with participants, this article demonstrates how marketing practices encourage the proliferation of multiple sexualities.

Simulations are employed widely as teaching tools in political science, yet evidence of their pedagogical effectiveness, in comparison to other methods of instruction, is mixed. The assessment of learning outcomes is often a secondary concern in simulation design, and the qualitative and quantitative methods used to evaluate outcomes are frequently based on faulty paradigms of the learning process and inappropriate indicators. Correctly incorporating assessment into simulation design requires that an instructor identify whether a simulation should produce positive changes in students' substantive knowledge, skills, and/or affective characteristics. The simulation must then be assessed in ways that accurately measure whether these goals have been achieved. Proper assessment can help demonstrate that simulations are productive tools for learning and that their popularity in the classroom is justified.

Abstract The objective was to systematically review the medical literature and comprehensively summarize clinical research performed on biomarkers for pediatric traumatic brain injury (TBI) and to summarize the studies that have assessed serum biomarkers acutely in determining intracranial lesions on CT in children with TBI. The search strategy included a literature search of PubMed,(®) MEDLINE,(®) and the Cochrane Database from 1966 to August 2011, as well as a review of reference lists of identified studies. Search terms used included pediatrics, children, traumatic brain injury, and biomarkers. Any article with biomarkers of traumatic brain injury as a primary focus and containing a pediatric population was included. The search initially identified 167 articles. Of these, 49 met inclusion and exclusion criteria and were critically reviewed. The median sample size was 58 (interquartile range 31-101). The majority of the articles exclusively studied children (36, 74%), and 13 (26%) were studies that included both children and adults in different proportions. There were 99 different biomarkers measured in these 49 studies, and the five most frequently examined biomarkers were S100B (27 studies), neuron-specific enolase (NSE) (15 studies), interleukin (IL)-6 (7 studies), myelin basic protein (MBP) (6 studies), and IL-8 (6 studies). There were six studies that assessed the relationship between serum markers and CT lesions. Two studies found that NSE levels ≥15 ng/mL within 24 h of TBI was associated with intracranial lesions. Four studies using serum S100B were conflicting: two studies found no association with intracranial lesions and two studies found a weak association. The flurry of research in the area over the last decade is encouraging but is limited by small sample sizes, variable practices in sample collection, inconsistent biomarker-related data elements, and disparate outcome measures. Future studies of biomarkers for pediatric TBI will require rigorous and more uniform research methodology, common data elements, and consistent performance measures.

Measuring panels of protein biomarkers offer a new personalized approach to early cancer detection, disease monitoring and patients' response to therapy. Multiplex electrochemical methods are uniquely positioned to provide faster, more sensitive, point of care (POC) devices to detect protein biomarkers for clinical diagnosis. Nanomaterials-based electrochemical methods offer sensitivity needed for early cancer detection. This review discusses recent advances in multiplex electrochemical immunosensors for cancer diagnostics and disease monitoring. Different electrochemical strategies including enzyme-based immunoarrays, nanoparticle-based immunoarrays and electrochemiluminescence methods are discussed. Many of these methods have been integrated into microfluidic systems, but measurement of more than 2-4 protein markers in a small single serum sample is still a challenge. For POC applications, a simple, low cost method is required. Major challenges in multiplexed microfluidic immunoassays are reagent additions and washing steps that require creative engineering solutions. 3-D printed microfluidics and paper-based microfluidic devices are also explored.

Role-playing simulations are frequently claimed to be effective pedagogical tools in the teaching of international relations (IR); however, there is a surprising lack of empirical evidence on their classroom utility. The assessment of simulations remains mostly anecdotal, and some recent research has found little to no statistically significant improvements in quantitative measures of academic performance among students who participated in them [for example, International Studies Perspectives (2006), vol. 7, pp. 395; International Studies Perspectives (2008), vol. 9, pp. 75–89]. Scant research has been conducted on how role-playing simulations might affect students’ perceptions of the instructor’s teaching. This paper investigates whether a simulation had statistically significant effect on students’ exam scores in an IR course or on student teaching evaluation scores.

Objectives: Urolithins, ellagitannin-gut microbial-derived metabolites, have been reported to mediate pomegranate’s neuroprotective effects against Alzheimer’s disease (AD), but there are limited data on their effects against neuroinflammation. Herein, we: (1) evaluated whether urolithins (urolithins A and B and their methylated derivatives) attenuate neuroinflammation in murine BV-2 microglia and human SH-SY5Y neurons, and (2) evaluated hippocampus of transgenic AD (R1.40) mice administered a pomegranate extract (PE; 100 or 200 mg/kg/day for 3 weeks) for inflammatory biomarkers.Methods: Effects of urolithins (10 μM) on inflammatory biomarkers were evaluated in lipopolysaccharide (LPS)-stimulated BV-2 microglia. In a non-contact co-culture cell model, SH-SY5Y cell viability was assessed after exposure to media collected from LPS-BV-2 cells treated with or without urolithins. Effects of urolithins on apoptosis and caspase 3/7 and 9 release from H2O2-induced oxidative stress of BV-2 and SH-SY5Y cells were assessed. Hippocampal tissues of vehicle and PE-treated transgenic R1.40 mice were evaluated for gene expression of inflammatory biomarkers by qRT-PCR.Results: Urolithins decreased media levels of nitric oxide, interleukin 6 (IL-6), prostaglandin E2, and tumor necrosis factor alpha from LPS-BV-2 microglia. In the co-culture cell model, media from LPS-BV-2 cells treated with urolithins preserved SH-SY5Y cell viability greater than media from cells treated without urolithins. Urolithins mitigated apoptosis and caspase 3/7 and 9 release from H2O2-induced oxidative stress of BV-2 and SH-SY5Y cells. While not statistically significant, inflammatory biomarkers (TNF-α, COX-2, IL-1, and IL-6) appeared to follow a decreasing trend in the hippocampus of high-dose PE-treated animals compared to controls.Discussion: The attenuation of neuroinflammation by urolithins may contribute, in part, toward pomegranate’s neuroprotective effects against AD.

Political protests have a long history throughout the world, but the rise of contemporary forms of communication such as ubiquitous cellphone and video recording technology and both formal and info...

The year 2007 marks the 10th anniversary of the introduction of granular computing research. We have experienced the emergence and growth of granular computing research in the past ten years. It is essential to explore and review the progress made in the field of granular computing. We use two popular databases, ISI's Web of Science and IEEE Digital Library to conduct our research. We study the current status, the trends and the future direction of granular computing and identify prolific authors, impact authors, and the most impact papers in the past decade.

This phenomenological study describes the essential structure of the lived experience of adult male survivors of childhood sexual abuse by clergy (AMSCSABC). A purposive sample of seven AMSCSABC related their subjective experiences in semistructured interviews. Colaizzi's (1978) phenomenological method was used for data analysis. Survivors describe a bifurcated rage and spiritual distress that pervades their entire "lifebeing." Learning about AMSCSABC will assist nurses to identify potential risk factors of childhood sexual abuse by clergy (CSABC), design prevention strategies, and enhance empathy for a healing relationship.

The learning and communication style of the Millennial generation is through multi-media. Also known as the Net Generation, they have been raised in an era of instant access Their common method of contact is text messaging and instant messaging as well as cell phones. Learning for them has moved into web-based tools such as web-ct, online journals, and i-pod downloads. The attitudes of Millennial generation students from a small private college were measured regarding the style of learning they use, prefer and which method they perceive has resulted most successfully in their acquiring and retaining knowledge.

Horizontal violence (HV), or nonphysical intergroup conflict expressed in overt and covert behaviors of hostility, is pervasive in nursing and has been discussed in the literature for more than two decades. It is costly and has potentially devastating effects including high nurse turnover rates, increased illness, decreased productivity, and decreased quality of patient care. Recognizing how these behaviors are established and sustained is necessary if nurses are to overcome these types of behaviors. This mixed methods study used an online survey to examine 76 hospital nurses' experiences and responses to episodes of HV as well as its effects on job performance. Seven of these nurses answered more in-depth questions during a follow-up interview. Nurses in this study recognize HV as a phenomenon that occurred early in their careers as novice nurses. The literature suggests that these behaviors are evident during nursing education. The academic environment is an ideal place to teach the skills necessary to respond appropriately to HV with peer support being essential. Nurses also reported that manager and staff support and workplace education were the most helpful in reducing HV. Increased workload and stress and HV being accepted practice on the unit were factors identified as most important in promoting HV. Further, nurses cited reasons why they continue in their jobs after episodes of HV. Intervention studies are needed to test effective ways of reducing this very difficult behavior among nurses in the workplace.

A novel electrochemical immunosensor for the detection of matrix metalloproteinase-3 (MMP-3), a cancer biomarker protein, based on vertically aligned single-wall carbon nanotube (SWCNT) arrays is presented. Detection was based on a sandwich immunoassay consisting of horseradish peroxidase (14-16 labels) conjugated to a secondary antibody and/or a polymer bead loaded with multi-enzyme labels. Performance was optimized by effective minimization of non-specific binding (NSB) events using Bovine serum albumin (BSA), Tween-20 and optimization of the primary antibody and secondary antibody concentrations. Results provided a detection limit of 0.4 ng mL(-1) (7.7 pM) for the 14-16 label sensor protocol and 4 pg mL(-1) (77 fM) using a multiply enzyme labeled polymeric bead amplification strategy in 10 microL of calf serum. This immunosensor based on SWCNT arrays offers great promise for a rapid, simple, cost-effective method for clinical screening of cancer biomarkers for point-of-care diagnosis.

BACKGROUND: For many high-risk patients, accessing primary care is challenged by competing needs and priorities, socioeconomics, and other circumstances. The resulting lack of treatment engagement makes these vulnerable patient populations susceptible to poor health outcomes and an over-reliance on emergency department-based care. METHODS: We describe a quasi-experimental pre-post study examining a vulnerable population-based application of the patient-centered medical home applied to four high-risk groups: homeless veterans, cognitively impaired elderly, women veterans and patients with serious mental illness. We measured 6-month primary care, emergency department and inpatient care use and chronic disease management when care was based in a general internal medicine clinic (2006) and in a population-specific medical home (2008). RESULTS: Overall 457 patients were studied, assessing care use and outcomes for the last 6 months in each study year. Compared with 2006, in 2008 there was a significant increase in primary care use (p < 0.001) and improvement in chronic disease monitoring and diabetes control (2006 HBA1C: 8.5 vs. 2008 HBA1C 6.9) in all four groups. However, there was also an increase in both emergency department use and hospitalizations, albeit with shorter lengths of stay in 2008 compared with 2006. Most of the increased utilization was driven by a small proportion of patients in each group. CONCLUSION: Tailoring the medical home model to the specific needs and challenges facing high-risk populations can increase primary care utilization and improve chronic disease monitoring and diabetes management. More work is needed in directing this care model to reducing emergency department and inpatient use.

Thermal tolerance of an organism depends on both the ability to dynamically adjust to a thermal stress and preparatory developmental processes that enhance thermal resistance. However, the extent to which standing genetic variation in thermal tolerance alleles influence dynamic stress responses vs. preparatory processes is unknown. Here, using the model species Drosophila melanogaster, we used a combination of Genome Wide Association mapping (GWAS) and transcriptomic profiling to characterize whether genes associated with thermal tolerance are primarily involved in dynamic stress responses or preparatory processes that influence physiological condition at the time of thermal stress. To test our hypotheses, we measured the critical thermal minimum (CTmin) and critical thermal maximum (CTmax) of 100 lines of the Drosophila Genetic Reference Panel (DGRP) and used GWAS to identify loci that explain variation in thermal limits. We observed greater variation in lower thermal limits, with CTmin ranging from 1.81 to 8.60°C, while CTmax ranged from 38.74 to 40.64°C. We identified 151 and 99 distinct genes associated with CTmin and CTmax, respectively, and there was strong support that these genes are involved in both dynamic responses to thermal stress and preparatory processes that increase thermal resistance. Many of the genes identified by GWAS were involved in the direct transcriptional response to thermal stress (72/151 for cold; 59/99 for heat), and overall GWAS candidates were more likely to be differentially expressed than other genes. Further, several GWAS candidates were regulatory genes that may participate in the regulation of stress responses, and gene ontologies related to development and morphogenesis were enriched, suggesting many of these genes influence thermal tolerance through effects on development and physiological status. Overall, our results suggest that thermal tolerance alleles can influence both dynamic plastic responses to thermal stress and preparatory processes that improve thermal resistance. These results also have utility for directly comparing GWAS and transcriptomic approaches for identifying candidate genes associated with thermal tolerance.